chr17-19703134-C-T

Variant names:

• chr17-19703134-C-T
• NM_001099646.3:c.1052G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099646.3(SLC47A2):​c.1052G>A​(p.Ser351Asn) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC47A2 NM_001099646.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.808
• Publications: 0 publications found

Genes affected

SLC47A2 (HGNC:26439): (solute carrier family 47 member 2) This gene encodes a protein belonging to a family of transporters involved in excretion of toxic electrolytes, both endogenous and exogenous, through urine and bile. This transporter family shares homology with the bacterial MATE (multidrug and toxin extrusion) protein family responsible for drug resistance. This gene is one of two members of the MATE transporter family located near each other on chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099646.3. 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
	SLC47A2	NM_001099646.3	MANE Select	c.1052G>A	p.Ser351Asn	missense	Exon 12 of 17	NP_001093116.1	Q86VL8-3
	SLC47A2	NM_152908.5		c.1160G>A	p.Ser387Asn	missense	Exon 12 of 17	NP_690872.2
	SLC47A2	NM_001256663.3		c.1094G>A	p.Ser365Asn	missense	Exon 13 of 18	NP_001243592.1	Q86VL8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A2	ENST00000433844.4	TSL:5 MANE Select	c.1052G>A	p.Ser351Asn	missense	Exon 12 of 17	ENSP00000391848.3	Q86VL8-3
	SLC47A2	ENST00000325411.9	TSL:1	c.1160G>A	p.Ser387Asn	missense	Exon 12 of 17	ENSP00000326671.5	Q86VL8-1
	SLC47A2	ENST00000350657.9	TSL:1	c.1094G>A	p.Ser365Asn	missense	Exon 13 of 18	ENSP00000338084.6	Q86VL8-4

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	Benign	0.19
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.81
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.084
Sift	Benign	0.083	T
Sift4G	Uncertain	0.060	T
Polyphen		0.27	B
Vest4		0.23
MutPred		0.34		Loss of catalytic residue at S387 (P = 0.1368)
MVP		0.040
MPC		0.16
ClinPred		0.27	T
GERP RS		1.4
Varity_R		0.070
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr17-19606447;