chr1-169921762-C-T

Position:

chr1-169921762-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001375830.1(KIFAP3):c.2330G>A(p.Trp777*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000862 in 1,613,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

KIFAP3
NM_001375830.1 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

Variant links:

Genes affected

KIFAP3 (HGNC:17060): (kinesin associated protein 3) The small G protein GDP dissociation stimulator (smg GDS) is a regulator protein having two activities on a group of small G proteins including the Rho and Rap1 family members and Ki-Ras; one is to stimulate their GDP/GTP exchange reactions, and the other is to inhibit their interactions with membranes. The protein encoded by this gene contains 9 'Armadillo' repeats and interacts with the smg GDS protein through these repeats. This protein, which is highly concentrated around the endoplasmic reticulum, is phosphorylated by v-src, and this phosphorylation reduces the affinity of the protein for smg GDS. It is thought that this protein serves as a linker between human chromosome-associated polypeptide (HCAP) and KIF3A/B, a kinesin superfamily protein in the nucleus, and that it plays a role in the interaction of chromosomes with an ATPase motor protein. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

KIFAP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFAP3	NM_014970.4 linkuse as main transcript	c.2293G>A	p.Gly765Ser	missense_variant	20/20	ENST00000361580.7	NP_055785.2	Q92845-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIFAP3	ENST00000361580.7 linkuse as main transcript	c.2293G>A	p.Gly765Ser	missense_variant	20/20	1	NM_014970.4	ENSP00000354560.2	Q92845-1
KIFAP3	ENST00000367767.5 linkuse as main transcript	c.2161G>A	p.Gly721Ser	missense_variant	19/19	1		ENSP00000356741.1	Q92845-2
KIFAP3	ENST00000367765.5 linkuse as main transcript	c.2173G>A	p.Gly725Ser	missense_variant	20/20	2		ENSP00000356739.1	Q92845-3
KIFAP3	ENST00000538366.5 linkuse as main transcript	c.2059G>A	p.Gly687Ser	missense_variant	21/21	2		ENSP00000444622.1	Q92845-4

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000123

AC:

AN:

251124

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.00179

Gnomad AMR exome

AF:

0.0000579

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000500

AC:

AN:

1461198

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.000134

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:

0.00000810

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000434

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000252

Hom.:

Bravo

AF:

0.000514

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 02, 2024

The c.2293G>A (p.G765S) alteration is located in exon 20 (coding exon 20) of the KIFAP3 gene. This alteration results from a G to A substitution at nucleotide position 2293, causing the glycine (G) at amino acid position 765 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.080

.;.;T;.

Eigen

Benign

0.028

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.42

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.26

T;T;T;T

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.27

.;.;B;.

Vest4

0.27

MVP

0.49

MPC

0.33

ClinPred

0.042

GERP RS

5.8

Varity_R

0.053

gMVP

0.80

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