9-112889606-C-T

Variant names:

• chr9-112889606-C-T
• NM_033051.4:c.1076G>A

Variant summary

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

The NM_033051.4(SLC46A2):​c.1076G>A​(p.Gly359Glu) 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: 32)
• Consequence: SLC46A2 NM_033051.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.974

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.1076G>A	p.Gly359Glu	missense_variant	Exon 1 of 4	ENST00000374228.5	NP_149040.3
SLC46A2	XM_047423640.1	c.957+119G>A		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.1076G>A	p.Gly359Glu	missense_variant	Exon 1 of 4	1	NM_033051.4	ENSP00000363345.4
SLC46A2	ENST00000491462.2	n.957+119G>A		intron_variant	Intron 1 of 3	5		ENSP00000474847.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1076G>A (p.G359E) alteration is located in exon 1 (coding exon 1) of the SLC46A2 gene. This alteration results from a G to A substitution at nucleotide position 1076, causing the glycine (G) at amino acid position 359 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.78	N
REVEL	Uncertain	0.30
Sift	Benign	0.12	T
Sift4G	Benign	0.080	T
Polyphen		0.90	P
Vest4		0.50
MutPred		0.77		Loss of glycosylation at S360 (P = 0.0725);
MVP		0.77
MPC		0.97
ClinPred		0.87	D
GERP RS		4.1
Varity_R		0.26
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-115651886;