12-66347757-ATT-ATTT

Variant names:

• chr12-66347757-A-AT
• rs35499444
• NM_001366722.1:c.*1261dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001366722.1(GRIP1):​c.*1261dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (311 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: GRIP1 NM_001366722.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 0.240
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Fraser syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Fraser syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-66347757-A-AT is Benign according to our data. Variant chr12-66347757-A-AT is described in ClinVar as Likely_benign. ClinVar VariationId is 310275.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366722.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	NM_001366722.1	MANE Select	c.*1261dupA		3_prime_UTR	Exon 25 of 25	NP_001353651.1	Q9Y3R0-1
	GRIP1	NM_001379345.1		c.*1261dupA		3_prime_UTR	Exon 25 of 25	NP_001366274.1
	GRIP1	NM_001439322.1		c.*1261dupA		3_prime_UTR	Exon 24 of 24	NP_001426251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000359742.9	TSL:5 MANE Select	c.*1261dupA		3_prime_UTR	Exon 25 of 25	ENSP00000352780.4	Q9Y3R0-1
	GRIP1	ENST00000398016.7	TSL:1	c.*1261dupA		3_prime_UTR	Exon 24 of 24	ENSP00000381098.3	Q9Y3R0-3
	GRIP1	ENST00000696989.1		c.*1261dupA		3_prime_UTR	Exon 23 of 23	ENSP00000513025.1	A0A8V8TLS6

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0454 AC: 6867 AN: 151330 Hom.: 311 Cov.: 0 AF XY: 0.0441 AC XY: 3257 AN XY: 73906

African (AFR) AF: 0.113 AC: 4662 AN: 41244

American (AMR) AF: 0.0216 AC: 328 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 128 AN: 3462

East Asian (EAS) AF: 0.00991 AC: 51 AN: 5144

South Asian (SAS) AF: 0.0299 AC: 144 AN: 4810

European-Finnish (FIN) AF: 0.0142 AC: 148 AN: 10444

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0194 AC: 1316 AN: 67716

Other (OTH) AF: 0.0382 AC: 80 AN: 2096

Alfa AF: 0.0119 Hom.: 504

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	1	Fraser syndrome 1 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35499444; hg19: chr12-66741537;