chrX-48981451-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020137.5(GRIPAP1):c.1795G>A(p.Gly599Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000888 in 112,646 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)
Consequence
GRIPAP1
NM_020137.5 missense
NM_020137.5 missense
Scores
6
3
6
Clinical Significance
Conservation
PhyloP100: 5.15
Genes affected
GRIPAP1 (HGNC:18706): (GRIP1 associated protein 1) This gene encodes a guanine nucleotide exchange factor for the Ras family of small G proteins (RasGEF). The encoded protein interacts in a complex with glutamate receptor interacting protein 1 (GRIP1) and plays a role in the regulation of AMPA receptor function. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GRIPAP1 | NM_020137.5 | c.1795G>A | p.Gly599Arg | missense_variant | 20/26 | ENST00000376423.8 | NP_064522.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GRIPAP1 | ENST00000376423.8 | c.1795G>A | p.Gly599Arg | missense_variant | 20/26 | 1 | NM_020137.5 | ENSP00000365606 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000888 AC: 1AN: 112646Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34796
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GnomAD4 exome Cov.: 32
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GnomAD4 genome AF: 0.00000888 AC: 1AN: 112646Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34796
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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 | May 14, 2024 | The c.1795G>A (p.G599R) alteration is located in exon 20 (coding exon 20) of the GRIPAP1 gene. This alteration results from a G to A substitution at nucleotide position 1795, causing the glycine (G) at amino acid position 599 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;T;T
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
REVEL
Benign
Sift4G
Benign
T;T;T
Polyphen
1.0
.;.;D
Vest4
MutPred
0.22
.;.;Gain of MoRF binding (P = 0.0211);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at