5-132702097-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001300791.2(KIF3A):c.1874G>A(p.Arg625Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00017 in 1,608,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

KIF3A
NM_001300791.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.86

Variant links:

Genes affected

KIF3A (HGNC:6319): (kinesin family member 3A) Enables protein phosphatase binding activity; small GTPase binding activity; and spectrin binding activity. Involved in protein localization to cell junction and protein transport. Located in centriole and centrosome. Part of kinesin II complex. Colocalizes with spindle microtubule. [provided by Alliance of Genome Resources, Apr 2022]

KIF3A links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, KIF3A

BP4

Computational evidence support a benign effect (MetaRNN=0.033771336).

BP6

Variant 5-132702097-C-T is Benign according to our data. Variant chr5-132702097-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2319353.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF3A	NM_001300791.2 linkuse as main transcript	c.1874G>A	p.Arg625Gln	missense_variant	15/19	ENST00000403231.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF3A	ENST00000403231.6 linkuse as main transcript	c.1874G>A	p.Arg625Gln	missense_variant	15/19	2	NM_001300791.2
	ENST00000628061.1 linkuse as main transcript	n.111+12263C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

251100

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000169

AC:

246

AN:

1456480

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

111

AN XY:

724558

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000199

Gnomad4 OTH exome

AF:

0.000200

GnomAD4 genome

AF:

0.000178

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000189

Hom.:

Bravo

AF:

0.000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.21

T;T;T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.0057

MetaRNN

Benign

0.034

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.3

N;.;.;.

MutationTaster

Benign

0.90

D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

0.88

N;N;.;N

REVEL

Benign

0.077

Sift

Benign

0.80

T;T;.;T

Sift4G

Benign

0.82

T;T;T;T

Polyphen

0.0

B;.;.;B

Vest4

0.16

MVP

0.043

MPC

0.79

ClinPred

0.053

GERP RS

4.7

Varity_R

0.043

gMVP

0.073

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