NM_001080423.4:c.*4452T>G

Variant names:

• chr3-14489213-A-C
• rs9036
• NM_001080423.4:c.*4452T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080423.4(GRIP2):​c.*4452T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRIP2 NM_001080423.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 0 publications found

Genes affected

GRIP2 (HGNC:23841): (glutamate receptor interacting protein 2) Predicted to enable protein C-terminus binding activity. Predicted to be involved in several processes, including neurotransmitter receptor transport, endosome to postsynaptic membrane; positive regulation of AMPA glutamate receptor clustering; and positive regulation of excitatory postsynaptic potential. Predicted to act upstream of or within Notch signaling pathway; artery smooth muscle contraction; and positive regulation of blood pressure. Predicted to be located in cytoplasm; dendritic shaft; and neuron spine. Predicted to be active in glutamatergic synapse and postsynaptic density. [provided by Alliance of Genome Resources, Apr 2022]

SLC6A6 (HGNC:11052): (solute carrier family 6 member 6) This gene encodes a multi-pass membrane protein that is a member of a family of sodium and chloride-ion dependent transporters. The encoded protein transports taurine and beta-alanine. There is a pseudogene for this gene on chromosome 21. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

SLC6A6 Gene-Disease associations (from GenCC):

• hypotaurinemic retinal degeneration and cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP2	NM_001080423.4	c.*4452T>G		3_prime_UTR_variant	Exon 24 of 24	ENST00000621039.5	NP_001073892.3
SLC6A6	NM_003043.6	c.*4206A>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000622186.5	NP_003034.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIP2	ENST00000621039.5	c.*4452T>G		3_prime_UTR_variant	Exon 24 of 24	1	NM_001080423.4	ENSP00000478352.1
SLC6A6	ENST00000622186.5	c.*4206A>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_003043.6	ENSP00000480890.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.7
DANN	Benign	0.86
PhyloP100		1.1

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

Other links and lift over

dbSNP: rs9036; hg19: chr3-14530721;