12-46366911-C-G

Variant names:

• chr12-46366911-C-G
• rs780192393
• NM_018976.5:c.516G>C

Variant summary

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

The NM_018976.5(SLC38A2):​c.516G>C​(p.Glu172Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC38A2 NM_018976.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.80
• Publications: 0 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 2 ACMG points.

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

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.516G>C	p.Glu172Asp	missense	Exon 7 of 16	NP_061849.2
	SLC38A2	NM_001307936.2		c.216G>C	p.Glu72Asp	missense	Exon 6 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.516G>C	p.Glu172Asp	missense	Exon 7 of 16	ENSP00000256689.5	Q96QD8-1
	SLC38A2	ENST00000612232.1	TSL:1	c.216G>C	p.Glu72Asp	missense	Exon 4 of 13	ENSP00000482873.1	Q96QD8-2
	SLC38A2	ENST00000901221.1		c.516G>C	p.Glu172Asp	missense	Exon 6 of 15	ENSP00000571280.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.041	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.56		Gain of ubiquitination at K170 (P = 0.0972)
MVP		0.10
MPC		0.71
ClinPred		0.99	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.80
Mutation Taster		=67/33	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: rs780192393; hg19: chr12-46760694;