9-83806370-T-C

Position:

chr9-83806370-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025211.4(GKAP1):c.148A>G(p.Thr50Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 1,578,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GKAP1
NM_025211.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06609756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GKAP1	NM_025211.4 linkuse as main transcript	c.148A>G	p.Thr50Ala	missense_variant	3/13	ENST00000376371.7	NP_079487.2	Q5VSY0-1
GKAP1	NM_001135953.2 linkuse as main transcript	c.148A>G	p.Thr50Ala	missense_variant	3/12		NP_001129425.1	Q5VSY0-2
GKAP1	XM_005252241.3 linkuse as main transcript	c.148A>G	p.Thr50Ala	missense_variant	3/13		XP_005252298.1	Q5VSY0-1
GKAP1	XM_011519058.3 linkuse as main transcript	c.148A>G	p.Thr50Ala	missense_variant	4/14		XP_011517360.1	Q5VSY0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GKAP1	ENST00000376371.7 linkuse as main transcript	c.148A>G	p.Thr50Ala	missense_variant	3/13	1	NM_025211.4	ENSP00000365550.2	Q5VSY0-1
GKAP1	ENST00000376365.7 linkuse as main transcript	c.148A>G	p.Thr50Ala	missense_variant	3/12	1		ENSP00000365544.3	Q5VSY0-2
GKAP1	ENST00000485742.5 linkuse as main transcript	c.148A>G	p.Thr50Ala	missense_variant	3/3	3		ENSP00000417621.1	C9J9D2
GKAP1	ENST00000388782.8 linkuse as main transcript	n.148A>G		non_coding_transcript_exon_variant	5/11	2		ENSP00000373434.4	B4DXS0

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000101

AC:

AN:

198798

Hom.:

AF XY:

0.00000941

AC XY:

AN XY:

106258

show subpopulations

Gnomad AFR exome

AF:

0.000159

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000105

AC:

AN:

1425948

Hom.:

Cov.:

AF XY:

0.00000849

AC XY:

AN XY:

706314

show subpopulations

Gnomad4 AFR exome

AF:

0.000340

Gnomad4 AMR exome

AF:

0.0000257

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:

0.00

Gnomad4 OTH exome

AF:

0.0000507

GnomAD4 genome

AF:

0.000112

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000410

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000132

ExAC

AF:

0.0000166

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 25, 2024

The c.148A>G (p.T50A) alteration is located in exon 3 (coding exon 1) of the GKAP1 gene. This alteration results from a A to G substitution at nucleotide position 148, causing the threonine (T) at amino acid position 50 to be replaced by an alanine (A). 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

0.059

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.017

T;.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.070

N;N;N

REVEL

Benign

0.045

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.85

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.048

MutPred

0.14

Loss of phosphorylation at T50 (P = 0.0165);Loss of phosphorylation at T50 (P = 0.0165);Loss of phosphorylation at T50 (P = 0.0165);

MVP

0.14

MPC

0.063

ClinPred

0.016

GERP RS

2.7

Varity_R

0.036

gMVP

0.087

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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