Variant 9-83768925-T-G 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.631A>C(p.Asn211His) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GKAP1
NM_025211.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

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:

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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=0.2210314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GKAP1	NM_025211.4 linkuse as main transcript	c.631A>C	p.Asn211His	missense_variant	8/13	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.631A>C	p.Asn211His	missense_variant	8/13	1	NM_025211.4	ENSP00000365550	P1	Q5VSY0-1
GKAP1	ENST00000376365.7 linkuse as main transcript	c.585+11457A>C		intron_variant		1		ENSP00000365544		Q5VSY0-2
GKAP1	ENST00000388782.8 linkuse as main transcript	c.*317A>C		3_prime_UTR_variant, NMD_transcript_variant	11/11	2		ENSP00000373434

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458316

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725662

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 29, 2023

The c.631A>C (p.N211H) alteration is located in exon 8 (coding exon 6) of the GKAP1 gene. This alteration results from a A to C substitution at nucleotide position 631, causing the asparagine (N) at amino acid position 211 to be replaced by a histidine (H). 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

0.085

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.090

Eigen

Benign

-0.0035

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.78

M_CAP

Benign

0.0039

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Benign

0.10

Sift4G

Benign

0.19

Polyphen

0.20

Vest4

0.36

MutPred

0.35

Gain of catalytic residue at L213 (P = 0.086);

MVP

0.27

MPC

0.082

ClinPred

0.62

GERP RS

4.7

Varity_R

0.19

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over