rs181365280

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The NM_001366722.1(GRIP1):c.2327G>A(p.Gly776Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000384 in 1,614,116 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G776G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000072 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 1 hom. )

Consequence

GRIP1
NM_001366722.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 4.03

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 -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13789913).

BP6

Variant 12-66392445-C-T is Benign according to our data. Variant chr12-66392445-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435390.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIP1	NM_001366722.1 linkuse as main transcript	c.2327G>A	p.Gly776Glu	missense_variant	19/25	ENST00000359742.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIP1	ENST00000359742.9 linkuse as main transcript	c.2327G>A	p.Gly776Glu	missense_variant	19/25	5	NM_001366722.1	P1	Q9Y3R0-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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:

0.0000321

AC:

AN:

249442

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000256

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000579

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 14, 2016

- -

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.2171G>A (p.G724E) alteration is located in exon 18 (coding exon 18) of the GRIP1 gene. This alteration results from a G to A substitution at nucleotide position 2171, causing the glycine (G) at amino acid position 724 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.46

Cadd

Uncertain

Dann

Benign

0.95

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

T;T;T;T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.70

D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.35

N;N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.25

T;T;T;T;T

Sift4G

Benign

0.40

T;T;.;T;.

Polyphen

0.0

B;B;B;.;.

Vest4

0.063

MVP

0.18

MPC

0.43

ClinPred

0.023

GERP RS

4.8

Varity_R

0.12

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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