dbSNP rs17102531: GRIP1:p.Ala322Ser (chr12-66463002-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS1

The NM_001366722.1(GRIP1):c.964G>T(p.Ala322Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000991 in 1,613,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

GRIP1
NM_001366722.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.88

Variant links:

Genes affected

GRIP1 (HGNC:18708): (glutamate receptor interacting protein 1) This gene encodes a member of the glutamate receptor interacting protein family. The encoded scaffold protein binds to and mediates the trafficking and membrane organization of a number of transmembrane proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, May 2010]

GRIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14898667).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000592 (9/152076) while in subpopulation AFR AF= 0.000217 (9/41470). AF 95% confidence interval is 0.000113. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP1	NM_001366722.1 link	c.964G>T	p.Ala322Ser	missense_variant	Exon 9 of 25	ENST00000359742.9	NP_001353651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000359742.9 link	c.964G>T	p.Ala322Ser	missense_variant	Exon 9 of 25	5	NM_001366722.1	ENSP00000352780.4		Q9Y3R0-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249260

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.000323

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ExAC

AF:

0.0000331

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Benign

0.92

DEOGEN2

Benign

0.16

.;T;T;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.99

L;L;.;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.7

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.15

T;T;T;T;T

Sift4G

Benign

0.35

T;T;.;T;.

Polyphen

0.0040

B;B;B;.;.

Vest4

0.14

MutPred

0.47

Gain of catalytic residue at T324 (P = 0.1051);Gain of catalytic residue at T324 (P = 0.1051);Gain of catalytic residue at T324 (P = 0.1051);.;.;

MVP

0.32

MPC

0.34

ClinPred

0.11

GERP RS

4.2

Varity_R

0.36

gMVP

0.22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over