rs966852445

Variant names:

• chr17-19678898-C-G
• rs966852445
• NM_001099646.3:c.1489G>C

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.1489G>C​(p.Gly497Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000446 in 1,569,578 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC47A2 NM_001099646.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.533
• Publications: 1 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: Myriad Women’s Health, G2P, Labcorp Genetics (formerly Invitae), Orphanet

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=0.117939174).

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.1489G>C	p.Gly497Arg	missense	Exon 17 of 17	NP_001093116.1	Q86VL8-3
	SLC47A2	NM_152908.5		c.1597G>C	p.Gly533Arg	missense	Exon 17 of 17	NP_690872.2
	SLC47A2	NM_001256663.3		c.1531G>C	p.Gly511Arg	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.1489G>C	p.Gly497Arg	missense	Exon 17 of 17	ENSP00000391848.3	Q86VL8-3
	SLC47A2	ENST00000325411.9	TSL:1	c.1597G>C	p.Gly533Arg	missense	Exon 17 of 17	ENSP00000326671.5	Q86VL8-1
	SLC47A2	ENST00000350657.9	TSL:1	c.1531G>C	p.Gly511Arg	missense	Exon 18 of 18	ENSP00000338084.6	Q86VL8-4

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1417382 Hom.: 0 Cov.: 30 AF XY: 0.00000285 AC XY: 2 AN XY: 701206

African (AFR) AF: 0.0000308 AC: 1 AN: 32434

American (AMR) AF: 0.00 AC: 0 AN: 37866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25360

East Asian (EAS) AF: 0.00 AC: 0 AN: 37284

South Asian (SAS) AF: 0.00 AC: 0 AN: 81864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1087912

Other (OTH) AF: 0.00 AC: 0 AN: 58618

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74350

African (AFR) AF: 0.0000965 AC: 4 AN: 41440

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	0.18
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.5
DANN	Benign	0.50
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.53
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.027
Sift	Benign	0.40	T
Sift4G	Benign	0.40	T
Polyphen		0.59	P
Vest4		0.29
MVP		0.11
MPC		0.48
ClinPred		0.31	T
GERP RS		3.0
Varity_R		0.035
gMVP		0.16

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: rs966852445; hg19: chr17-19582211;