chr9-112889606-C-T

Variant names:

• chr9-112889606-C-T
• rs188435024
• NM_033051.4:c.1076G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

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_033051.4. 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
	SLC46A2	NM_033051.4	MANE Select	c.1076G>A	p.Gly359Glu	missense	Exon 1 of 4	NP_149040.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC46A2	ENST00000374228.5	TSL:1 MANE Select	c.1076G>A	p.Gly359Glu	missense	Exon 1 of 4	ENSP00000363345.4	Q9BY10
	SLC46A2	ENST00000868988.1		c.967+109G>A		intron	N/A	ENSP00000539047.1
	SLC46A2	ENST00000491462.2	TSL:5	n.957+119G>A		intron	N/A	ENSP00000474847.1	S4R3Y2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.89
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
PhyloP100		0.97
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
Mutation Taster		=80/20	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: rs188435024; hg19: chr9-115651886;