chr12-46364427-C-A

Variant names:

• chr12-46364427-C-A
• rs770450547
• NM_018976.5:c.835G>T

Variant summary

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

The NM_018976.5(SLC38A2):​c.835G>T​(p.Asp279Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,449,572 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D279N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: SLC38A2 NM_018976.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66
• Publications: 1 publications found

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018976.5. 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
	SLC38A2	NM_018976.5	MANE Select	c.835G>T	p.Asp279Tyr	missense	Exon 10 of 16	NP_061849.2
	SLC38A2	NM_001307936.2		c.535G>T	p.Asp179Tyr	missense	Exon 9 of 15	NP_001294865.1	Q96QD8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A2	ENST00000256689.10	TSL:1 MANE Select	c.835G>T	p.Asp279Tyr	missense	Exon 10 of 16	ENSP00000256689.5	Q96QD8-1
	SLC38A2	ENST00000612232.1	TSL:1	c.535G>T	p.Asp179Tyr	missense	Exon 7 of 13	ENSP00000482873.1	Q96QD8-2
	SLC38A2	ENST00000901221.1		c.835G>T	p.Asp279Tyr	missense	Exon 9 of 15	ENSP00000571280.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000377 AC: 9 AN: 238724 AF XY: 0.0000542

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: 0.0000186 AC: 27 AN: 1449572 Hom.: 0 Cov.: 32 AF XY: 0.0000222 AC XY: 16 AN XY: 720936

African (AFR) AF: 0.00 AC: 0 AN: 32498

American (AMR) AF: 0.00 AC: 0 AN: 41090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25562

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.000312 AC: 26 AN: 83450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108520

Other (OTH) AF: 0.00 AC: 0 AN: 59864

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	-0.22	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.73
MutPred		0.52		Loss of disorder (P = 0.0283)
MVP		0.043
MPC		0.73
ClinPred		0.57	D
GERP RS		5.7
Varity_R		0.49
gMVP		0.87
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs770450547; hg19: chr12-46758210;