ENST00000377890.6:c.34G>A

Variant names:

• chr11-62856303-G-A
• rs144685406
• ENST00000377890.6:c.34G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000377890.6(SLC3A2):​c.34G>A​(p.Val12Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V12F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC3A2 ENST00000377890.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• Publications: 1 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]

SNHG1 (HGNC:32688): (small nucleolar RNA host gene 1) This locus represents a small nucleolar RNA host gene that produces multiple alternatively spliced long non-coding RNAs. This gene is upregulated in cancers and is thought to act as promoter of cell proliferation. This transcript negatively regulates tumor suppressor genes such as tumor protein p53. Expression of this locus may be a marker of tumor progression. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09338772).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377890.6. 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
	SLC3A2	NM_001012662.3		c.34G>A	p.Val12Ile	missense	Exon 1 of 12	NP_001012680.1	P08195-5
	SLC3A2	NM_002394.6		c.34G>A	p.Val12Ile	missense	Exon 1 of 12	NP_002385.3
	SLC3A2	NM_001012664.3		c.34G>A	p.Val12Ile	missense	Exon 1 of 10	NP_001012682.1	P08195-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A2	ENST00000377890.6	TSL:1	c.34G>A	p.Val12Ile	missense	Exon 1 of 12	ENSP00000367122.2	P08195-1
	SLC3A2	ENST00000377889.6	TSL:1	c.34G>A	p.Val12Ile	missense	Exon 1 of 10	ENSP00000367121.2	P08195-3
	SLC3A2	ENST00000538084.2	TSL:3	c.34G>A	p.Val12Ile	missense	Exon 1 of 13	ENSP00000440001.2	P08195-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251248 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461144 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726728

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111428

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	0.0043	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.093	T
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	0.0	N
PhyloP100		2.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.31	T
Polyphen		0.052	B
Vest4		0.17
MutPred		0.20		Loss of glycosylation at S14 (P = 0.1073)
MVP		0.31
MPC		0.54
ClinPred		0.34	T
GERP RS		2.9
PromoterAI		0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.019
Mutation Taster		=99/1	polymorphism

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: rs144685406; hg19: chr11-62623775;