chr11-62856303-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001012662.3(SLC3A2):​c.34G>T​(p.Val12Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,613,406 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: SLC3A2 NM_001012662.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02323234).
• BS2: High AC in GnomAd4 at 50 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012662.3. 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>T	p.Val12Phe	missense	Exon 1 of 12	NP_001012680.1	P08195-5
	SLC3A2	NM_002394.6		c.34G>T	p.Val12Phe	missense	Exon 1 of 12	NP_002385.3
	SLC3A2	NM_001012664.3		c.34G>T	p.Val12Phe	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>T	p.Val12Phe	missense	Exon 1 of 12	ENSP00000367122.2	P08195-1
	SLC3A2	ENST00000377889.6	TSL:1	c.34G>T	p.Val12Phe	missense	Exon 1 of 10	ENSP00000367121.2	P08195-3
	SLC3A2	ENST00000538084.2	TSL:3	c.34G>T	p.Val12Phe	missense	Exon 1 of 13	ENSP00000440001.2	P08195-4

Frequencies

GnomAD3 genomes AF: 0.000328 AC: 50 AN: 152262 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000119 AC: 30 AN: 251248 AF XY: 0.0000810

Gnomad AFR exome AF: 0.00185

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461144 Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24 AN XY: 726728

African (AFR) AF: 0.00120 AC: 40 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: 0.00 AC: 0 AN: 1111428

Other (OTH) AF: 0.000116 AC: 7 AN: 60352

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152262 Hom.: 1 Cov.: 33 AF XY: 0.000229 AC XY: 17 AN XY: 74388

African (AFR) AF: 0.00109 AC: 45 AN: 41474

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00143 AC: 3 AN: 2094

Alfa AF: 0.000163 Hom.: 0

Bravo AF: 0.000434

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000140 AC: 17

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.023	T
MetaSVM	Uncertain	0.65	D
MutationAssessor	Benign	0.0	N
PhyloP100		2.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.40	N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		0.87	P
Vest4		0.32
MVP		0.48
MPC		1.3
ClinPred		0.19	T
GERP RS		2.9
PromoterAI		-0.017	Neutral
Varity_R		0.20
gMVP		0.077
Mutation Taster		=100/0	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;