12-66347757-A-ATT

Position:

• chr12-66347757-A-ATT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS1

The NM_001366722.1(GRIP1):​c.*1260_*1261dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: GRIP1 NM_001366722.1 3_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.240

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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 12-66347757-A-ATT is Benign according to our data. Variant chr12-66347757-A-ATT is described in ClinVar as [Likely_benign]. Clinvar id is 3029431.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000436 (66/151342) while in subpopulation AFR AF= 0.00145 (60/41250). AF 95% confidence interval is 0.00116. There are 0 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIP1	NM_001366722.1	c.*1260_*1261dupAA		3_prime_UTR_variant	25/25	ENST00000359742.9	NP_001353651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000359742	c.*1260_*1261dupAA		3_prime_UTR_variant	25/25	5	NM_001366722.1	ENSP00000352780.4
GRIP1	ENST00000398016	c.*1260_*1261dupAA		3_prime_UTR_variant	24/24	1		ENSP00000381098.3
GRIP1	ENST00000696989	c.*1260_*1261dupAA		3_prime_UTR_variant	23/23			ENSP00000513025.1

Frequencies

GnomAD3 genomes AF: 0.000417 AC: 63 AN: 151224 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000482

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.000436 AC: 66 AN: 151342 Hom.: 0 Cov.: 0 AF XY: 0.000392 AC XY: 29 AN XY: 73908

Gnomad4 AFR AF: 0.00145

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.000477

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GRIP1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35499444; hg19: chr12-66741537;