9-83799256-G-C
Position:
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
NM_025211.4 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: -0.0210
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]
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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 |
---|---|---|---|---|---|---|---|---|
GKAP1 | NM_025211.4 | c.289C>G | p.Pro97Ala | missense_variant | 4/13 | ENST00000376371.7 | NP_079487.2 | |
GKAP1 | NM_001135953.2 | c.289C>G | p.Pro97Ala | missense_variant | 4/12 | NP_001129425.1 | ||
GKAP1 | XM_005252241.3 | c.289C>G | p.Pro97Ala | missense_variant | 4/13 | XP_005252298.1 | ||
GKAP1 | XM_011519058.3 | c.289C>G | p.Pro97Ala | missense_variant | 5/14 | XP_011517360.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GKAP1 | ENST00000376371.7 | c.289C>G | p.Pro97Ala | missense_variant | 4/13 | 1 | NM_025211.4 | ENSP00000365550 | P1 | |
GKAP1 | ENST00000376365.7 | c.289C>G | p.Pro97Ala | missense_variant | 4/12 | 1 | ENSP00000365544 | |||
GKAP1 | ENST00000388782.8 | c.289C>G | p.Pro97Ala | missense_variant, NMD_transcript_variant | 6/11 | 2 | ENSP00000373434 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246190Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133162
GnomAD3 exomes
AF:
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1
AN:
246190
Hom.:
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AC XY:
1
AN XY:
133162
Gnomad AFR exome
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GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
AF:
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 submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at