9-83799256-G-C

Variant summary

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

The NM_025211.4(GKAP1):​c.289C>G​(p.Pro97Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

GKAP1
NM_025211.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0210
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]

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=0.014611185).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GKAP1NM_025211.4 linkuse as main transcriptc.289C>G p.Pro97Ala missense_variant 4/13 ENST00000376371.7 NP_079487.2
GKAP1NM_001135953.2 linkuse as main transcriptc.289C>G p.Pro97Ala missense_variant 4/12 NP_001129425.1
GKAP1XM_005252241.3 linkuse as main transcriptc.289C>G p.Pro97Ala missense_variant 4/13 XP_005252298.1
GKAP1XM_011519058.3 linkuse as main transcriptc.289C>G p.Pro97Ala missense_variant 5/14 XP_011517360.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GKAP1ENST00000376371.7 linkuse as main transcriptc.289C>G p.Pro97Ala missense_variant 4/131 NM_025211.4 ENSP00000365550 P1Q5VSY0-1
GKAP1ENST00000376365.7 linkuse as main transcriptc.289C>G p.Pro97Ala missense_variant 4/121 ENSP00000365544 Q5VSY0-2
GKAP1ENST00000388782.8 linkuse as main transcriptc.289C>G p.Pro97Ala missense_variant, NMD_transcript_variant 6/112 ENSP00000373434

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000406
AC:
1
AN:
246190
Hom.:
0
AF XY:
0.00000751
AC XY:
1
AN XY:
133162
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:
0.00000891
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsSep 16, 2021The c.289C>G (p.P97A) alteration is located in exon 4 (coding exon 2) of the GKAP1 gene. This alteration results from a C to G substitution at nucleotide position 289, causing the proline (P) at amino acid position 97 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
0.056
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.39
DANN
Benign
0.34
DEOGEN2
Benign
0.022
T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.015
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-1.1
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.59
N;N
REVEL
Benign
0.062
Sift
Benign
0.89
T;T
Sift4G
Benign
0.97
T;T
Polyphen
0.0
B;B
Vest4
0.063
MutPred
0.19
Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP
0.10
MPC
0.063
ClinPred
0.045
T
GERP RS
-2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.019
gMVP
0.029

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.

Other links and lift over

dbSNP: rs781224571; hg19: chr9-86414171; API