chr11-62881135-G-A

Variant names:

• chr11-62881135-G-A
• rs772779788
• NM_001013251.3:c.112G>A

Variant summary

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

The NM_001013251.3(SLC3A2):​c.112G>A​(p.Glu38Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,004 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E38Q) 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: 8.31
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.112G>A	p.Glu38Lys	missense	Exon 1 of 9	NP_001013269.1	P08195-2
	SLC3A2	NM_001012662.3		c.418G>A	p.Glu140Lys	missense	Exon 4 of 12	NP_001012680.1	P08195-5
	SLC3A2	NM_002394.6		c.415G>A	p.Glu139Lys	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.112G>A	p.Glu38Lys	missense	Exon 1 of 9	ENSP00000340815.7	P08195-2
	SLC3A2	ENST00000377890.6	TSL:1	c.415G>A	p.Glu139Lys	missense	Exon 4 of 12	ENSP00000367122.2	P08195-1
	SLC3A2	ENST00000377889.6	TSL:1	c.229G>A	p.Glu77Lys	missense	Exon 2 of 10	ENSP00000367121.2	P08195-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452004 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721382

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

American (AMR) AF: 0.00 AC: 0 AN: 41780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25752

East Asian (EAS) AF: 0.00 AC: 0 AN: 39328

South Asian (SAS) AF: 0.00 AC: 0 AN: 84446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108690

Other (OTH) AF: 0.00 AC: 0 AN: 60102

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.085	D
MutationAssessor	Benign	1.8	L
PhyloP100		8.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.55
Sift	Benign	0.042	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.67
MutPred		0.34		Gain of MoRF binding (P = 0.0045)
MVP		0.90
MPC		1.5
ClinPred		0.98	D
GERP RS		5.0
PromoterAI		-0.031	Neutral
Varity_R		0.41
gMVP		0.65
Mutation Taster		=59/41	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: rs772779788; hg19: chr11-62648607;