rs773814719

Variant names:

• chr12-46362364-T-A
• NM_018976.5:c.1342A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-46362364-T-A
• chr12-46362364-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018976.5(SLC38A2):​c.1342A>T​(p.Met448Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,610 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. M448V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC38A2 NM_018976.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.61

Genes affected

SLC38A2 (HGNC:13448): (solute carrier family 38 member 2) Enables neutral amino acid:sodium symporter activity. Involved in several processes, including amino acid transport; cellular response to arsenite(3-); and positive regulation of RNA splicing. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39472383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A2	NM_018976.5	c.1342A>T	p.Met448Leu	missense_variant	Exon 15 of 16	ENST00000256689.10	NP_061849.2
SLC38A2	NM_001307936.2	c.1042A>T	p.Met348Leu	missense_variant	Exon 14 of 15		NP_001294865.1
SLC38A2	XM_047429019.1	c.1042A>T	p.Met348Leu	missense_variant	Exon 12 of 13		XP_047284975.1
SLC38A2	XM_047429020.1	c.*213A>T		downstream_gene_variant			XP_047284976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A2	ENST00000256689.10	c.1342A>T	p.Met448Leu	missense_variant	Exon 15 of 16	1	NM_018976.5	ENSP00000256689.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459610 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.027	T;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Benign	0.23
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.92	P;B;B
Vest4		0.58
MutPred		0.70		Gain of glycosylation at S444 (P = 0.1752);.;.;
MVP		0.33
MPC		0.23
ClinPred		0.94	D
GERP RS		6.1
Varity_R		0.31
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-46756147;