Variant 9-83780397-A-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.570T>G(p.Ile190Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000924 in 1,298,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

GKAP1
NM_025211.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

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=0.1058974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GKAP1	NM_025211.4 linkuse as main transcript	c.570T>G	p.Ile190Met	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.570T>G	p.Ile190Met	missense_variant	7/13	1	NM_025211.4	ENSP00000365550	P1	Q5VSY0-1
GKAP1	ENST00000376365.7 linkuse as main transcript	c.570T>G	p.Ile190Met	missense_variant	7/12	1		ENSP00000365544		Q5VSY0-2
GKAP1	ENST00000388782.8 linkuse as main transcript	c.*256T>G		3_prime_UTR_variant, NMD_transcript_variant	10/11	2		ENSP00000373434

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150512

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000871

AC:

AN:

1147630

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

575796

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:

0.0000102

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150512

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73466

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000296

Gnomad4 OTH

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

Dec 15, 2023

The c.570T>G (p.I190M) alteration is located in exon 7 (coding exon 5) of the GKAP1 gene. This alteration results from a T to G substitution at nucleotide position 570, causing the isoleucine (I) at amino acid position 190 to be replaced by a methionine (M). 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

0.073

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.038

T;.

Eigen

Benign

-0.094

Eigen_PC

Benign

0.090

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.56

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.30

N;N

REVEL

Benign

0.053

Sift

Benign

0.079

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.19

B;B

Vest4

0.28

MutPred

0.083

Loss of methylation at K192 (P = 0.1303);Loss of methylation at K192 (P = 0.1303);

MVP

0.27

MPC

0.077

ClinPred

0.50

GERP RS

5.2

Varity_R

0.15

gMVP

0.031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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