Variant 1-169992194-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_014970.4(KIFAP3):c.1245C>T(p.Arg415=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,583,798 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 3 hom. )

Consequence

KIFAP3
NM_014970.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.403

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 1-169992194-G-A is Benign according to our data. Variant chr1-169992194-G-A is described in ClinVar as [Benign]. Clinvar id is 3050553.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.403 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFAP3	NM_014970.4 linkuse as main transcript	c.1245C>T	p.Arg415=	synonymous_variant	11/20	ENST00000361580.7	NP_055785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIFAP3	ENST00000361580.7 linkuse as main transcript	c.1245C>T	p.Arg415=	synonymous_variant	11/20	1	NM_014970.4	ENSP00000354560	P1	Q92845-1
KIFAP3	ENST00000367767.5 linkuse as main transcript	c.1113C>T	p.Arg371=	synonymous_variant	10/19	1		ENSP00000356741		Q92845-2
KIFAP3	ENST00000367765.5 linkuse as main transcript	c.1125C>T	p.Arg375=	synonymous_variant	11/20	2		ENSP00000356739		Q92845-3
KIFAP3	ENST00000538366.5 linkuse as main transcript	c.1011C>T	p.Arg337=	synonymous_variant	12/21	2		ENSP00000444622		Q92845-4

Frequencies

GnomAD3 genomes

AF:

0.000382

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000660

AC:

152

AN:

230356

Hom.:

AF XY:

0.000599

AC XY:

AN XY:

125262

show subpopulations

Gnomad AFR exome

AF:

0.0000687

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.000736

GnomAD4 exome

AF:

0.000340

AC:

487

AN:

1431786

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

236

AN XY:

711920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000124

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.0000528

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.000382

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.000400

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIFAP3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.3

DANN

Benign

0.58

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