9-112889811-T-G

Variant names:

• chr9-112889811-T-G
• rs1423434735
• NM_033051.4:c.871A>C

Variant summary

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

The NM_033051.4(SLC46A2):​c.871A>C​(p.Ile291Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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: 0.169

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30710006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC46A2	NM_033051.4	c.871A>C	p.Ile291Leu	missense_variant	Exon 1 of 4	ENST00000374228.5	NP_149040.3
SLC46A2	XM_047423640.1	c.871A>C	p.Ile291Leu	missense_variant	Exon 1 of 3		XP_047279596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC46A2	ENST00000374228.5	c.871A>C	p.Ile291Leu	missense_variant	Exon 1 of 4	1	NM_033051.4	ENSP00000363345.4
SLC46A2	ENST00000491462.2	n.871A>C		non_coding_transcript_exon_variant	Exon 1 of 4	5		ENSP00000474847.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000193 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.0017
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.19
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.90	P
Vest4		0.27
MVP		0.43
MPC		0.39
ClinPred		0.82	D
GERP RS		3.3
Varity_R		0.23
gMVP		0.42

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: rs1423434735; hg19: chr9-115652091;