Variant 9-83784723-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025211.4(GKAP1):c.554A>G(p.His185Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,436,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

GKAP1
NM_025211.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.28

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14480436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GKAP1	NM_025211.4 linkuse as main transcript	c.554A>G	p.His185Arg	missense_variant	6/13	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.554A>G	p.His185Arg	missense_variant	6/13	1	NM_025211.4	ENSP00000365550	P1	Q5VSY0-1
GKAP1	ENST00000376365.7 linkuse as main transcript	c.554A>G	p.His185Arg	missense_variant	6/12	1		ENSP00000365544		Q5VSY0-2
GKAP1	ENST00000388782.8 linkuse as main transcript	c.*240A>G		3_prime_UTR_variant, NMD_transcript_variant	9/11	2		ENSP00000373434

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000427

AC:

AN:

234106

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126808

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:

0.00000913

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1436454

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.09e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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

Apr 24, 2023

The c.554A>G (p.H185R) alteration is located in exon 6 (coding exon 4) of the GKAP1 gene. This alteration results from a A to G substitution at nucleotide position 554, causing the histidine (H) at amino acid position 185 to be replaced by an arginine (R). 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

0.077

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.033

T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.037

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0035

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.90

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.066

Sift

Benign

0.14

T;T

Sift4G

Uncertain

0.039

D;D

Polyphen

0.0070

B;B

Vest4

0.35

MutPred

0.17

Gain of MoRF binding (P = 0.0225);Gain of MoRF binding (P = 0.0225);

MVP

0.31

MPC

0.081

ClinPred

0.69

GERP RS

5.2

Varity_R

0.19

gMVP

0.098

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