rs8037349

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198525.3(KIF7):c.1102A>G(p.Thr368Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 1,528,112 control chromosomes in the GnomAD database, including 622,120 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 61568 hom., cov: 33)

Exomes 𝑓: 0.90 ( 560552 hom. )

Consequence

KIF7
NM_198525.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -0.0580

Publications

24 publications found

Variant links:

Genes affected

KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]

KIF7 Gene-Disease associations (from GenCC):

acrocallosal syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hydrolethalus syndrome 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
hydrolethalus syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
multiple epiphyseal dysplasia, Al-Gazali type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
orofaciodigital syndrome type 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KIF7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.2696605E-7).

BP6

Variant 15-89648596-T-C is Benign according to our data. Variant chr15-89648596-T-C is described in ClinVar as Benign. ClinVar VariationId is 96649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.1102A>G	p.Thr368Ala	missense_variant	Exon 5 of 19	ENST00000394412.8	NP_940927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
KIF7	ENST00000394412.8 link	c.1102A>G	p.Thr368Ala	missense_variant	Exon 5 of 19	5	NM_198525.3	ENSP00000377934.3
KIF7	ENST00000445906.1 link	n.*761A>G		non_coding_transcript_exon_variant	Exon 5 of 5	1		ENSP00000395906.1
KIF7	ENST00000445906.1 link	n.*761A>G		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000395906.1
KIF7	ENST00000696512.1 link	c.1225A>G	p.Thr409Ala	missense_variant	Exon 5 of 19			ENSP00000512678.1

Frequencies

GnomAD3 genomes

AF:

0.902

AC:

135810

AN:

150546

Hom.:

61530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.960

Gnomad AMI

AF:

0.950

Gnomad AMR

AF:

0.796

Gnomad ASJ

AF:

0.835

Gnomad EAS

AF:

0.740

Gnomad SAS

AF:

0.853

Gnomad FIN

AF:

0.878

Gnomad MID

AF:

0.901

Gnomad NFE

AF:

0.913

Gnomad OTH

AF:

0.897

GnomAD2 exomes

AF:

0.855

AC:

111890

AN:

130850

AF XY:

0.861

show subpopulations

Gnomad AFR exome

AF:

0.966

Gnomad AMR exome

AF:

0.735

Gnomad ASJ exome

AF:

0.841

Gnomad EAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.874

Gnomad NFE exome

AF:

0.914

Gnomad OTH exome

AF:

0.867

GnomAD4 exome

AF:

0.901

AC:

1240843

AN:

1377476

Hom.:

560552

Cov.:

AF XY:

0.901

AC XY:

612086

AN XY:

679702

show subpopulations

African (AFR)

AF:

0.963

AC:

30082

AN:

31248

American (AMR)

AF:

0.745

AC:

26345

AN:

35376

Ashkenazi Jewish (ASJ)

AF:

0.848

AC:

21048

AN:

24830

East Asian (EAS)

AF:

0.698

AC:

24619

AN:

35268

South Asian (SAS)

AF:

0.876

AC:

69266

AN:

79030

European-Finnish (FIN)

AF:

0.880

AC:

30084

AN:

34176

Middle Eastern (MID)

AF:

0.877

AC:

4887

AN:

5570

European-Non Finnish (NFE)

AF:

0.915

AC:

983153

AN:

1074626

Other (OTH)

AF:

0.896

AC:

51359

AN:

57352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

5964

11929

17893

23858

29822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21090

42180

63270

84360

105450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.902

AC:

135891

AN:

150636

Hom.:

61568

Cov.:

AF XY:

0.897

AC XY:

66042

AN XY:

73608

show subpopulations

African (AFR)

AF:

0.960

AC:

39696

AN:

41352

American (AMR)

AF:

0.797

AC:

12061

AN:

15142

Ashkenazi Jewish (ASJ)

AF:

0.835

AC:

2891

AN:

3464

East Asian (EAS)

AF:

0.741

AC:

3796

AN:

5126

South Asian (SAS)

AF:

0.853

AC:

4119

AN:

4830

European-Finnish (FIN)

AF:

0.878

AC:

8678

AN:

9888

Middle Eastern (MID)

AF:

0.893

AC:

259

AN:

290

European-Non Finnish (NFE)

AF:

0.913

AC:

61649

AN:

67532

Other (OTH)

AF:

0.893

AC:

1876

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

681

1362

2043

2724

3405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.907

Hom.:

13632

Bravo

AF:

0.896

TwinsUK

AF:

0.912

AC:

3383

ALSPAC

AF:

0.917

AC:

3533

ESP6500AA

AF:

0.966

AC:

1327

ESP6500EA

AF:

0.904

AC:

2869

ExAC

AF:

0.879

AC:

14612

Asia WGS

AF:

0.794

AC:

2753

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 29, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Acrocallosal syndrome

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hydrolethalus syndrome 2

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

KIF7-related disorder

Benign:1

Sep 09, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Multiple epiphyseal dysplasia, Al-Gazali type

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

2.3

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.094

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.12

MetaRNN

Benign

7.3e-7

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.12

PhyloP100

-0.058

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.69

REVEL

Benign

0.061

Sift

Benign

0.46

Sift4G

Benign

0.79

Polyphen

0.0

Vest4

0.025

MPC

0.018

ClinPred

0.0015

GERP RS

1.9

Varity_R

0.025

gMVP

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over