chrX-48987841-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020137.5(GRIPAP1):​c.985G>A​(p.Glu329Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 19)

Consequence

GRIPAP1
NM_020137.5 missense

Scores

4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12001526).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GRIPAP1NM_020137.5 linkuse as main transcriptc.985G>A p.Glu329Lys missense_variant 13/26 ENST00000376423.8 NP_064522.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GRIPAP1ENST00000376423.8 linkuse as main transcriptc.985G>A p.Glu329Lys missense_variant 13/261 NM_020137.5 ENSP00000365606 P3Q4V328-1

Frequencies

GnomAD3 genomes
Cov.:
19
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
19

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 GeneticsDec 14, 2023The c.985G>A (p.E329K) alteration is located in exon 13 (coding exon 13) of the GRIPAP1 gene. This alteration results from a G to A substitution at nucleotide position 985, causing the glutamic acid (E) at amino acid position 329 to be replaced by a lysine (K). 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
0.13
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.038
T;T
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.3
.;L
MutationTaster
Benign
0.51
D;D;D;D
PrimateAI
Uncertain
0.60
T
REVEL
Benign
0.032
Sift4G
Benign
0.19
T;T
Polyphen
0.0070
.;B
Vest4
0.13
MutPred
0.30
.;Gain of ubiquitination at E329 (P = 0.0045);
MVP
0.31
ClinPred
0.76
D
GERP RS
3.2
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.15
gMVP
0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-48844255; API