12-66347757-A-AT

Position:

• chr12-66347757-A-AT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001366722.1(GRIP1):​c.*1261_*1262insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.045 (311 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: GRIP1 NM_001366722.1 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 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 Benign. Variant got -9 ACMG points.

• BP6: Variant 12-66347757-A-AT is Benign according to our data. Variant chr12-66347757-A-AT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 310275.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIP1	NM_001366722.1	c.*1261_*1262insA		3_prime_UTR_variant	25/25	ENST00000359742.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIP1	ENST00000359742.9	c.*1261_*1262insA		3_prime_UTR_variant	25/25	5	NM_001366722.1	P1
GRIP1	ENST00000398016.7	c.*1261_*1262insA		3_prime_UTR_variant	24/24	1
GRIP1	ENST00000696989.1	c.*1261_*1262insA		3_prime_UTR_variant	23/23

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6841 AN: 151210 Hom.: 310 Cov.: 0

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0370

Gnomad EAS AF: 0.00989

Gnomad SAS AF: 0.0297

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0386

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: 0.0454 AC: 6867 AN: 151330 Hom.: 311 Cov.: 0 AF XY: 0.0441 AC XY: 3257 AN XY: 73906

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0370

Gnomad4 EAS AF: 0.00991

Gnomad4 SAS AF: 0.0299

Gnomad4 FIN AF: 0.0142

Gnomad4 NFE AF: 0.0194

Gnomad4 OTH AF: 0.0382

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Fraser syndrome 1 Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs35499444; hg19: chr12-66741537;