Variant 9-83780393-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_025211.4(GKAP1):c.574A>G(p.Lys192Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00012 in 1,340,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

GKAP1
NM_025211.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

Variant links:

Genes affected

GKAP1 (HGNC:17496): (G kinase anchoring protein 1) This gene encodes a protein that is highly similar to the mouse cGMP-dependent protein kinase anchoring protein 42kDa. The mouse protein has been found to localize with the Golgi and recruit cGMP-dependent protein kinase I alpha to the Golgi in mouse testes. It is thought to play a role in germ cell development. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

GKAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35651565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GKAP1	NM_025211.4 linkuse as main transcript	c.574A>G	p.Lys192Glu	missense_variant	7/13	ENST00000376371.7	NP_079487.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GKAP1	ENST00000376371.7 linkuse as main transcript	c.574A>G	p.Lys192Glu	missense_variant	7/13	1	NM_025211.4	ENSP00000365550	P1	Q5VSY0-1
GKAP1	ENST00000376365.7 linkuse as main transcript	c.574A>G	p.Lys192Glu	missense_variant	7/12	1		ENSP00000365544		Q5VSY0-2
GKAP1	ENST00000388782.8 linkuse as main transcript	c.*260A>G		3_prime_UTR_variant, NMD_transcript_variant	10/11	2		ENSP00000373434

Frequencies

GnomAD3 genomes

AF:

0.0000535

AC:

AN:

149410

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000104

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000680

AC:

AN:

205824

Hom.:

AF XY:

0.0000800

AC XY:

AN XY:

112438

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

153

AN:

1191524

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

598110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000337

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:

0.000163

Gnomad4 OTH exome

AF:

0.0000617

GnomAD4 genome

AF:

0.0000535

AC:

AN:

149410

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72718

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000104

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000659

AC:

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

Mar 23, 2022

The c.574A>G (p.K192E) alteration is located in exon 7 (coding exon 5) of the GKAP1 gene. This alteration results from a A to G substitution at nucleotide position 574, causing the lysine (K) at amino acid position 192 to be replaced by a glutamic acid (E). 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

0.12

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

D;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.36

T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.20

Sift

Benign

0.21

T;D

Sift4G

Benign

0.44

T;T

Polyphen

1.0

D;D

Vest4

0.49

MutPred

0.18

Loss of ubiquitination at K192 (P = 6e-04);Loss of ubiquitination at K192 (P = 6e-04);

MVP

0.48

MPC

0.15

ClinPred

0.26

GERP RS

5.2

Varity_R

0.27

gMVP

0.085

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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