chr17-19678846-A-C

Variant names:

• chr17-19678846-A-C
• rs890426530
• NM_001099646.3:c.1541T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099646.3(SLC47A2):​c.1541T>G​(p.Val514Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,459,452 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V514M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: SLC47A2 NM_001099646.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0520
• 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]

ALDH3A2 (HGNC:403): (aldehyde dehydrogenase 3 family member A2) Aldehyde dehydrogenase isozymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This gene product catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid. Mutations in the gene cause Sjogren-Larsson syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ALDH3A2 Gene-Disease associations (from GenCC):

• Sjogren-Larsson syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05472654).

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.1541T>G	p.Val514Gly	missense	Exon 17 of 17	NP_001093116.1	Q86VL8-3
	SLC47A2	NM_152908.5		c.1649T>G	p.Val550Gly	missense	Exon 17 of 17	NP_690872.2
	SLC47A2	NM_001256663.3		c.1583T>G	p.Val528Gly	missense	Exon 18 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.1541T>G	p.Val514Gly	missense	Exon 17 of 17	ENSP00000391848.3	Q86VL8-3
	SLC47A2	ENST00000325411.9	TSL:1	c.1649T>G	p.Val550Gly	missense	Exon 17 of 17	ENSP00000326671.5	Q86VL8-1
	SLC47A2	ENST00000350657.9	TSL:1	c.1583T>G	p.Val528Gly	missense	Exon 18 of 18	ENSP00000338084.6	Q86VL8-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1459452 Hom.: 0 Cov.: 31 AF XY: 0.0000207 AC XY: 15 AN XY: 725806

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1110794

Other (OTH) AF: 0.0000663 AC: 4 AN: 60290

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

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	0.073
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.94
DANN	Benign	0.61
DEOGEN2	Benign	0.061	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.052
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.025
Sift	Benign	0.11	T
Sift4G	Benign	0.28	T
Polyphen		0.36	B
Vest4		0.085
MutPred		0.33		Loss of stability (P = 0.0079)
MVP		0.040
MPC		0.14
ClinPred		0.13	T
GERP RS		-1.9
Varity_R		0.088
gMVP		0.19
Mutation Taster		=95/5	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: rs890426530; hg19: chr17-19582159;