11-62881102-G-C

Variant names:

• chr11-62881102-G-C
• rs757945289
• NM_001013251.3:c.79G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001013251.3(SLC3A2):​c.79G>C​(p.Ala27Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,328 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A27S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC3A2 NM_001013251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26579088).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013251.3. 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_001013251.3	MANE Select	c.79G>C	p.Ala27Pro	missense	Exon 1 of 9	NP_001013269.1	P08195-2
	SLC3A2	NM_001012662.3		c.385G>C	p.Ala129Pro	missense	Exon 4 of 12	NP_001012680.1	P08195-5
	SLC3A2	NM_002394.6		c.382G>C	p.Ala128Pro	missense	Exon 4 of 12	NP_002385.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A2	ENST00000338663.12	TSL:1 MANE Select	c.79G>C	p.Ala27Pro	missense	Exon 1 of 9	ENSP00000340815.7	P08195-2
	SLC3A2	ENST00000377890.6	TSL:1	c.382G>C	p.Ala128Pro	missense	Exon 4 of 12	ENSP00000367122.2	P08195-1
	SLC3A2	ENST00000377889.6	TSL:1	c.196G>C	p.Ala66Pro	missense	Exon 2 of 10	ENSP00000367121.2	P08195-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000417 AC: 1 AN: 239612 AF XY: 0.00000773

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456328 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723650

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 43752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25810

East Asian (EAS) AF: 0.00 AC: 0 AN: 39512

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 85044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109798

Other (OTH) AF: 0.00 AC: 0 AN: 60168

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	-0.073	T
MutationAssessor	Benign	0.95	L
PhyloP100		4.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.86	N
REVEL	Uncertain	0.31
Sift	Benign	0.14	T
Sift4G	Benign	0.17	T
Polyphen		0.0070	B
Vest4		0.14
MutPred		0.24		Gain of loop (P = 0.0195)
MVP		0.75
MPC		0.92
ClinPred		0.77	D
GERP RS		4.8
PromoterAI		-0.046	Neutral
Varity_R		0.43
gMVP		0.30
Mutation Taster		=71/29	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: rs757945289; hg19: chr11-62648574;