rs9036

chr3-14489213-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080423.4(GRIP2):c.*4452T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,428 control chromosomes in the GnomAD database, including 2,495 homozygotes. 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: 𝑓 0.17 (2488 hom., cov: 32)
  • Exomes 𝑓: 0.17 (7 hom.)
• Consequence: GRIP2 NM_001080423.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIP2	NM_001080423.4	c.*4452T>C		3_prime_UTR_variant	24/24	ENST00000621039.5
SLC6A6	NM_003043.6	c.*4206A>G		3_prime_UTR_variant	15/15	ENST00000622186.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIP2	ENST00000621039.5	c.*4452T>C		3_prime_UTR_variant	24/24	1	NM_001080423.4	P2
SLC6A6	ENST00000622186.5	c.*4206A>G		3_prime_UTR_variant	15/15	1	NM_003043.6	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25786 AN: 151878 Hom.: 2488 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.174 AC: 75 AN: 432 Hom.: 7 Cov.: 0 AF XY: 0.158 AC XY: 41 AN XY: 260

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.170 AC: 25802 AN: 151996 Hom.: 2488 Cov.: 32 AF XY: 0.166 AC XY: 12354 AN XY: 74302

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.0962

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.203

Alfa AF: 0.207 Hom.: 7755

Bravo AF: 0.163

Asia WGS AF: 0.141 AC: 491 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	9.1
Dann	Benign	0.86

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: rs9036; hg19: chr3-14530721;