3-14489213-A-T

Variant names:

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

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>A 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. Variant has been reported in ClinVar as (no stars).

• 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: MODERATE, LIMITED Submitted by: PanelApp Australia, 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=-0.48).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080423.4. 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
	GRIP2	NM_001080423.4	MANE Select	c.*4452T>A		3_prime_UTR	Exon 24 of 24	NP_001073892.3	Q9C0E4-1
	SLC6A6	NM_003043.6	MANE Select	c.*4206A>T		3_prime_UTR	Exon 15 of 15	NP_003034.2	P31641-1
	SLC6A6	NM_001134367.3		c.*4206A>T		3_prime_UTR	Exon 15 of 15	NP_001127839.2	Q59GD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP2	ENST00000621039.5	TSL:1 MANE Select	c.*4452T>A		3_prime_UTR	Exon 24 of 24	ENSP00000478352.1	Q9C0E4-1
	SLC6A6	ENST00000622186.5	TSL:1 MANE Select	c.*4206A>T		3_prime_UTR	Exon 15 of 15	ENSP00000480890.1	P31641-1
	SLC6A6	ENST00000613060.4	TSL:1	c.*4206A>T		3_prime_UTR	Exon 15 of 15	ENSP00000481625.1	A0A087WY96

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.6
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;