chr15-89632842-C-A

Position:

chr15-89632842-C-A

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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

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:

KIF7 (HGNC:):

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=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 id is 96651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89632842-C-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
KIF7	NM_198525.3 linkuse as main transcript	c.2873G>T	p.Ser958Ile	missense_variant	14/19	ENST00000394412.8	NP_940927.2	Q2M1P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIF7	ENST00000394412.8 linkuse as main transcript	c.2873G>T	p.Ser958Ile	missense_variant	14/19	5	NM_198525.3	ENSP00000377934.3	Q2M1P5
KIF7	ENST00000696512.1 linkuse as main transcript	c.2996G>T	p.Ser999Ile	missense_variant	14/19			ENSP00000512678.1	A0A8Q3SIQ8
KIF7	ENST00000677187.1 linkuse as main transcript	n.547G>T		non_coding_transcript_exon_variant	2/7

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

GnomAD3 exomes

AF:

0.515

AC:

124854

AN:

242292

Hom.:

33198

AF XY:

0.520

AC XY:

68259

AN XY:

131198

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 SAS exome

AF:

0.489

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

Gnomad4 AFR exome

AF:

0.444

Gnomad4 AMR exome

AF:

0.416

Gnomad4 ASJ exome

AF:

0.543

Gnomad4 EAS exome

AF:

0.310

Gnomad4 SAS exome

AF:

0.496

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.586

Gnomad4 OTH exome

AF:

0.537

GnomAD4 genome

AF:

0.521

AC:

79059

AN:

151776

Hom.:

20936

Cov.:

AF XY:

0.519

AC XY:

38523

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.448

Gnomad4 AMR

AF:

0.453

Gnomad4 ASJ

AF:

0.537

Gnomad4 EAS

AF:

0.336

Gnomad4 SAS

AF:

0.471

Gnomad4 FIN

AF:

0.612

Gnomad4 NFE

AF:

0.582

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.560

Hom.:

34176

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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 06, 2013	- -
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	-	- -
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+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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. -

Acrocallosal syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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

- -

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

0.15

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

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

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

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