rs3803530

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.2873G>T(p.Ser958Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,605,504 control chromosomes in the GnomAD database, including 253,262 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20936 hom., cov: 31)

Exomes 𝑓: 0.56 ( 232326 hom. )

Consequence

KIF7
NM_198525.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: 1.13

Publications

32 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=2.8204651E-5).

BP6

Variant 15-89632842-C-A is Benign according to our data. Variant chr15-89632842-C-A is described in ClinVar as Benign. ClinVar VariationId is 96651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.2873G>T	p.Ser958Ile	missense_variant	Exon 14 of 19	ENST00000394412.8	NP_940927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
KIF7	ENST00000394412.8 link	c.2873G>T	p.Ser958Ile	missense_variant	Exon 14 of 19	5	NM_198525.3	ENSP00000377934.3
KIF7	ENST00000696512.1 link	c.2996G>T	p.Ser999Ile	missense_variant	Exon 14 of 19			ENSP00000512678.1
KIF7	ENST00000677187.1 link	n.547G>T		non_coding_transcript_exon_variant	Exon 2 of 7

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79003

AN:

151658

Hom.:

20918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.611

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.471

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.509

GnomAD2 exomes

AF:

0.515

AC:

124854

AN:

242292

AF XY:

0.520

show subpopulations

Gnomad AFR exome

AF:

0.444

Gnomad AMR exome

AF:

0.409

Gnomad ASJ exome

AF:

0.541

Gnomad EAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.604

Gnomad NFE exome

AF:

0.580

Gnomad OTH exome

AF:

0.521

GnomAD4 exome

AF:

0.562

AC:

816529

AN:

1453728

Hom.:

232326

Cov.:

AF XY:

0.560

AC XY:

404995

AN XY:

723106

show subpopulations

African (AFR)

AF:

0.444

AC:

14852

AN:

33464

American (AMR)

AF:

0.416

AC:

18448

AN:

44380

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

14146

AN:

26036

East Asian (EAS)

AF:

0.310

AC:

12309

AN:

39670

South Asian (SAS)

AF:

0.496

AC:

42522

AN:

85738

European-Finnish (FIN)

AF:

0.607

AC:

28968

AN:

47734

Middle Eastern (MID)

AF:

0.451

AC:

2506

AN:

5552

European-Non Finnish (NFE)

AF:

0.586

AC:

650448

AN:

1110898

Other (OTH)

AF:

0.537

AC:

32330

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

21804

43607

65411

87214

109018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17744

35488

53232

70976

88720

<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:

0.521

AC:

79059

AN:

151776

Hom.:

20936

Cov.:

AF XY:

0.519

AC XY:

38523

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.448

AC:

18546

AN:

41390

American (AMR)

AF:

0.453

AC:

6922

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

1860

AN:

3464

East Asian (EAS)

AF:

0.336

AC:

1731

AN:

5154

South Asian (SAS)

AF:

0.471

AC:

2261

AN:

4800

European-Finnish (FIN)

AF:

0.612

AC:

6475

AN:

10578

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.582

AC:

39485

AN:

67808

Other (OTH)

AF:

0.509

AC:

1072

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1799

3597

5396

7194

8993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.555

Hom.:

80453

Bravo

AF:

0.505

TwinsUK

AF:

0.585

AC:

2168

ALSPAC

AF:

0.581

AC:

2240

ESP6500AA

AF:

0.466

AC:

2051

ESP6500EA

AF:

0.574

AC:

4933

ExAC

AF:

0.523

AC:

63524

Asia WGS

AF:

0.413

AC:

1440

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:16

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 06, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Acrocallosal syndrome

Benign:4

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

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

0.15

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

-0.084

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.79

MetaRNN

Benign

0.000028

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.29

PhyloP100

1.1

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.4

REVEL

Benign

0.098

Sift

Benign

0.28

Sift4G

Benign

0.32

Polyphen

0.0030

Vest4

0.084

MPC

0.021

ClinPred

1.0

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.15

Mutation Taster

=87/13

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

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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