rs8037349

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 made for transcript

Verdict is Benign. Variant got -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 id is 96649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89648596-T-C is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
KIF7	NM_198525.3 linkuse as main transcript	c.1102A>G	p.Thr368Ala	missense_variant	5/19	ENST00000394412.8	NP_940927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KIF7	ENST00000394412.8 linkuse as main transcript	c.1102A>G	p.Thr368Ala	missense_variant	5/19	5	NM_198525.3	ENSP00000377934	P2
KIF7	ENST00000445906.1 linkuse as main transcript	c.*761A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000395906
KIF7	ENST00000696512.1 linkuse as main transcript	c.1225A>G	p.Thr409Ala	missense_variant	5/19			ENSP00000512678	A2

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

GnomAD3 exomes

AF:

0.855

AC:

111890

AN:

130850

Hom.:

48367

AF XY:

0.861

AC XY:

60829

AN XY:

70690

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 SAS exome

AF:

0.871

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

Gnomad4 AFR exome

AF:

0.963

Gnomad4 AMR exome

AF:

0.745

Gnomad4 ASJ exome

AF:

0.848

Gnomad4 EAS exome

AF:

0.698

Gnomad4 SAS exome

AF:

0.876

Gnomad4 FIN exome

AF:

0.880

Gnomad4 NFE exome

AF:

0.915

Gnomad4 OTH exome

AF:

0.896

GnomAD4 genome

AF:

0.902

AC:

135891

AN:

150636

Hom.:

61568

Cov.:

AF XY:

0.897

AC XY:

66042

AN XY:

73608

show subpopulations

Gnomad4 AFR

AF:

0.960

Gnomad4 AMR

AF:

0.797

Gnomad4 ASJ

AF:

0.835

Gnomad4 EAS

AF:

0.741

Gnomad4 SAS

AF:

0.853

Gnomad4 FIN

AF:

0.878

Gnomad4 NFE

AF:

0.913

Gnomad4 OTH

AF:

0.893

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

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 29, 2018	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Acrocallosal syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hydrolethalus syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

KIF7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 09, 2022

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

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

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

MutationTaster

Benign

1.0

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

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