chr3-14489213-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP2	NM_001080423.4	MANE Select	c.*4452T>C		3_prime_UTR	Exon 24 of 24	NP_001073892.3
	SLC6A6	NM_003043.6	MANE Select	c.*4206A>G		3_prime_UTR	Exon 15 of 15	NP_003034.2
	SLC6A6	NR_103507.3		n.6239A>G		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

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

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

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) AF: 0.176 AC: 75 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.105 AC: 4347 AN: 41464

American (AMR) AF: 0.164 AC: 2511 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 792 AN: 3470

East Asian (EAS) AF: 0.0962 AC: 499 AN: 5186

South Asian (SAS) AF: 0.173 AC: 835 AN: 4814

European-Finnish (FIN) AF: 0.144 AC: 1513 AN: 10520

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14679 AN: 67958

Other (OTH) AF: 0.203 AC: 428 AN: 2108

Alfa AF: 0.200 Hom.: 14344

Bravo AF: 0.163

Asia WGS AF: 0.141 AC: 491 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.1
DANN	Benign	0.86
PhyloP100		1.1
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

Other links and lift over

dbSNP: rs9036; hg19: chr3-14530721;