rs189438534

Variant names:

• chr12-66432560-T-C
• NM_001366722.1:c.1756A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-66432560-T-C
• chr12-66432560-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001366722.1(GRIP1):​c.1756A>G​(p.Ile586Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,432,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I586L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GRIP1 NM_001366722.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.30

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30978507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP1	NM_001366722.1	c.1756A>G	p.Ile586Val	missense_variant	Exon 14 of 25	ENST00000359742.9	NP_001353651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000359742.9	c.1756A>G	p.Ile586Val	missense_variant	Exon 14 of 25	5	NM_001366722.1	ENSP00000352780.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432124 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 714264

Gnomad4 AFR exome AF: 0.00

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: 9.21e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;T;T;T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.6	.;M;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.91	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.052	T;D;T;T;D
Sift4G	Uncertain	0.0060	D;D;.;D;.
Polyphen		0.75	P;B;B;.;.
Vest4		0.44
MutPred		0.52		.;Gain of catalytic residue at S590 (P = 0);.;.;.;
MVP		0.29
MPC		0.55
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.35
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-66826340;