Variant X-48983860-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020137.5(GRIPAP1):c.1187G>A(p.Arg396Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000652 in 1,146,651 control chromosomes in the GnomAD database, including 1 homozygotes. There are 242 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., 21 hem., cov: 22)

Exomes 𝑓: 0.00064 ( 1 hom. 221 hem. )

Consequence

GRIPAP1
NM_020137.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17

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]

GRIPAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015335739).

BS2

High Hemizygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIPAP1	NM_020137.5 linkuse as main transcript	c.1187G>A	p.Arg396Gln	missense_variant	15/26	ENST00000376423.8	NP_064522.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIPAP1	ENST00000376423.8 linkuse as main transcript	c.1187G>A	p.Arg396Gln	missense_variant	15/26	1	NM_020137.5	ENSP00000365606	P3	Q4V328-1

Frequencies

GnomAD3 genomes

AF:

0.000738

AC:

AN:

111119

Hom.:

Cov.:

AF XY:

0.000630

AC XY:

AN XY:

33317

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000963

Gnomad ASJ

AF:

0.00303

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00134

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000801

AC:

147

AN:

183498

Hom.:

AF XY:

0.000780

AC XY:

AN XY:

67930

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00254

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00156

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000643

AC:

666

AN:

1035532

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

221

AN XY:

310608

show subpopulations

Gnomad4 AFR exome

AF:

0.0000396

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00258

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000189

Gnomad4 FIN exome

AF:

0.00138

Gnomad4 NFE exome

AF:

0.000689

Gnomad4 OTH exome

AF:

0.000386

GnomAD4 genome

AF:

0.000738

AC:

AN:

111119

Hom.:

Cov.:

AF XY:

0.000630

AC XY:

AN XY:

33317

show subpopulations

Gnomad4 AFR

AF:

0.0000327

Gnomad4 AMR

AF:

0.0000963

Gnomad4 ASJ

AF:

0.00303

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00134

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.000601

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00104

AC:

ExAC

AF:

0.000717

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000533

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

Mar 14, 2024

The c.1187G>A (p.R396Q) alteration is located in exon 15 (coding exon 15) of the GRIPAP1 gene. This alteration results from a G to A substitution at nucleotide position 1187, causing the arginine (R) at amino acid position 396 to be replaced by a glutamine (Q). 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

0.091

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

.;T;T

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;.;L

MutationTaster

Benign

0.74

N;N;N;N

PrimateAI

Benign

0.46

REVEL

Benign

0.063

Sift4G

Benign

0.72

T;T;T

Polyphen

0.80

.;.;P

Vest4

0.064

MVP

0.59

ClinPred

0.041

GERP RS

4.3

Varity_R

0.084

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over