12-66348261-GATAAT-G

Position:

• chr12-66348261-GATAAT-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366722.1(GRIP1):​c.*753_*757delATTAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000442 in 151,700 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GRIP1 NM_001366722.1 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.424

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIP1	NM_001366722.1	c.*753_*757delATTAT		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.*753_*757delATTAT		3_prime_UTR_variant	25/25	5	NM_001366722.1	ENSP00000352780.4
GRIP1	ENST00000398016	c.*753_*757delATTAT		3_prime_UTR_variant	24/24	1		ENSP00000381098.3
GRIP1	ENST00000696989	c.*753_*757delATTAT		3_prime_UTR_variant	23/23			ENSP00000513025.1

Frequencies

GnomAD3 genomes AF: 0.000442 AC: 67 AN: 151700 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000960

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.000442 AC: 67 AN: 151700 Hom.: 0 Cov.: 32 AF XY: 0.000365 AC XY: 27 AN XY: 74054

Gnomad4 AFR AF: 0.000194

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.000960

Alfa AF: 0.000712 Hom.: 0

Bravo AF: 0.000559

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fraser syndrome 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs886049793; hg19: chr12-66742041;