rs141865394

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_StrongBS1BS2

The NM_198525.3(KIF7):c.49C>T(p.Arg17Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000847 in 1,540,090 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0039 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 8 hom. )

Consequence

KIF7
NM_198525.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.09

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 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=0.011151433).

BP6

Variant 15-89652882-G-A is Benign according to our data. Variant chr15-89652882-G-A is described in ClinVar as [Benign]. Clinvar id is 129418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00393 (598/152342) while in subpopulation AFR AF = 0.0134 (556/41580). AF 95% confidence interval is 0.0125. There are 3 homozygotes in GnomAd4. There are 295 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.49C>T	p.Arg17Trp	missense_variant	Exon 2 of 19	ENST00000394412.8	NP_940927.2	Q2M1P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIF7	ENST00000394412.8 link	c.49C>T	p.Arg17Trp	missense_variant	Exon 2 of 19	5	NM_198525.3	ENSP00000377934.3	Q2M1P5
KIF7	ENST00000445906.1 link	n.49C>T		non_coding_transcript_exon_variant	Exon 2 of 5	1		ENSP00000395906.1	F8WD21
KIF7	ENST00000696512.1 link	c.172C>T	p.Arg58Trp	missense_variant	Exon 2 of 19			ENSP00000512678.1	A0A8Q3SIQ8

Frequencies

GnomAD3 genomes

AF:

0.00392

AC:

597

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00129

AC:

186

AN:

143638

AF XY:

0.00114

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.000486

Gnomad EAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000370

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.000509

AC:

707

AN:

1387748

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

305

AN XY:

683134

show subpopulations

Gnomad4 AFR exome

AF:

0.0167

AC:

524

AN:

31450

Gnomad4 AMR exome

AF:

0.00115

AC:

AN:

35548

Gnomad4 ASJ exome

AF:

0.000360

AC:

AN:

25034

Gnomad4 EAS exome

AF:

0.000562

AC:

AN:

35570

Gnomad4 SAS exome

AF:

0.0000380

AC:

AN:

78890

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

44962

Gnomad4 NFE exome

AF:

0.0000391

AC:

AN:

1073354

Gnomad4 Remaining exome

AF:

0.00111

AC:

AN:

57486

Heterozygous variant carriers

113

151

189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00393

AC:

598

AN:

152342

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0134

AC:

0.0133718

AN:

0.0133718

Gnomad4 AMR

AF:

0.00196

AC:

0.00196053

AN:

0.00196053

Gnomad4 ASJ

AF:

0.000288

AC:

0.000288184

AN:

0.000288184

Gnomad4 EAS

AF:

0.000965

AC:

0.000964878

AN:

0.000964878

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000588

AC:

0.0000587976

AN:

0.0000587976

Gnomad4 OTH

AF:

0.000945

AC:

0.00094518

AN:

0.00094518

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<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:

0.00142

Hom.:

Bravo

AF:

0.00500

ExAC

AF:

0.00154

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 13, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KIF7: BS1, BS2 -

not specified

Benign:2

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. -

Apr 25, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Acrocallosal syndrome

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.80

Eigen

Benign

-0.024

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.30

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.011

MetaSVM

Uncertain

0.36

MutationAssessor

Pathogenic

3.6

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.49

MVP

0.62

MPC

0.097

ClinPred

0.060

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.62

gMVP

0.53

Mutation Taster

=86/14

polymorphism

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over