9-112889670-C-G

Variant names:

• chr9-112889670-C-G
• rs376496916
• NM_033051.4:c.1012G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033051.4(SLC46A2):​c.1012G>C​(p.Val338Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC46A2 NM_033051.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95

Genes affected

SLC46A2 (HGNC:16055): (solute carrier family 46 member 2) Predicted to enable transmembrane transporter activity. Involved in positive regulation of nucleotide-binding activity oligomerization domain containing 1 signaling pathway. Predicted to be located in cell surface and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC46A2	NM_033051.4	c.1012G>C	p.Val338Leu	missense_variant	Exon 1 of 4	ENST00000374228.5	NP_149040.3
SLC46A2	XM_047423640.1	c.957+55G>C		intron_variant	Intron 1 of 2		XP_047279596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC46A2	ENST00000374228.5	c.1012G>C	p.Val338Leu	missense_variant	Exon 1 of 4	1	NM_033051.4	ENSP00000363345.4
SLC46A2	ENST00000491462.2	n.957+55G>C		intron_variant	Intron 1 of 3	5		ENSP00000474847.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.013	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.88	P
Vest4		0.37
MutPred		0.61		Loss of methylation at R343 (P = 0.1527);
MVP		0.71
MPC		0.86
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.33
gMVP		0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs376496916; hg19: chr9-115651950;