rs12274689

Variant names:

• chr11-62880793-C-A
• rs12274689
• ENST00000377890.6:c.299-226C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-62880793-C-A
• chr11-62880793-C-G
• chr11-62880793-C-T

Variant summary

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

The ENST00000377890.6(SLC3A2):​c.299-226C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 673,484 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SLC3A2 ENST00000377890.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 0 publications found

Genes affected

SLC3A2 (HGNC:11026): (solute carrier family 3 member 2) This gene is a member of the solute carrier family and encodes a cell surface, transmembrane protein. The protein exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. The encoded transporter plays a role in regulation of intracellular calcium levels and transports L-type amino acids. Alternatively spliced transcript variants, encoding different isoforms, have been characterized. [provided by RefSeq, Nov 2010]

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=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A2	NM_001012662.3	c.302-226C>A		intron_variant	Intron 3 of 11		NP_001012680.1
SLC3A2	NM_002394.6	c.299-226C>A		intron_variant	Intron 3 of 11		NP_002385.3
SLC3A2	NM_001012664.3	c.113-226C>A		intron_variant	Intron 1 of 9		NP_001012682.1
SLC3A2	NM_001013251.3	c.-231C>A		upstream_gene_variant		ENST00000338663.12	NP_001013269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC3A2	ENST00000338663.12	c.-231C>A		upstream_gene_variant		1	NM_001013251.3	ENSP00000340815.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000148 AC: 1 AN: 673484 Hom.: 0 Cov.: 9 AF XY: 0.00000296 AC XY: 1 AN XY: 338410

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16374

American (AMR) AF: 0.00 AC: 0 AN: 14918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14466

East Asian (EAS) AF: 0.00 AC: 0 AN: 29598

South Asian (SAS) AF: 0.00 AC: 0 AN: 42832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2398

European-Non Finnish (NFE) AF: 0.00000203 AC: 1 AN: 491818

Other (OTH) AF: 0.00 AC: 0 AN: 32700

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		-0.41
PromoterAI		-0.093	Neutral

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: rs12274689; hg19: chr11-62648265;