NM_001099646.3:c.1520A>C

Variant names:

• chr17-19678867-T-G
• rs764964844
• NM_001099646.3:c.1520A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001099646.3(SLC47A2):​c.1520A>C​(p.Tyr507Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,601,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SLC47A2 NM_001099646.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.883
• 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: Myriad Women’s Health, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.08861908).

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.1520A>C	p.Tyr507Ser	missense	Exon 17 of 17	NP_001093116.1	Q86VL8-3
	SLC47A2	NM_152908.5		c.1628A>C	p.Tyr543Ser	missense	Exon 17 of 17	NP_690872.2
	SLC47A2	NM_001256663.3		c.1562A>C	p.Tyr521Ser	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.1520A>C	p.Tyr507Ser	missense	Exon 17 of 17	ENSP00000391848.3	Q86VL8-3
	SLC47A2	ENST00000325411.9	TSL:1	c.1628A>C	p.Tyr543Ser	missense	Exon 17 of 17	ENSP00000326671.5	Q86VL8-1
	SLC47A2	ENST00000350657.9	TSL:1	c.1562A>C	p.Tyr521Ser	missense	Exon 18 of 18	ENSP00000338084.6	Q86VL8-4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000313 AC: 7 AN: 223640 AF XY: 0.00000827

Gnomad AFR exome AF: 0.0000720

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000612

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000119 AC: 173 AN: 1449388 Hom.: 0 Cov.: 31 AF XY: 0.000112 AC XY: 81 AN XY: 720030

African (AFR) AF: 0.0000301 AC: 1 AN: 33234

American (AMR) AF: 0.00 AC: 0 AN: 42784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25794

East Asian (EAS) AF: 0.00 AC: 0 AN: 39300

South Asian (SAS) AF: 0.00 AC: 0 AN: 84834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.000145 AC: 160 AN: 1105292

Other (OTH) AF: 0.000201 AC: 12 AN: 59790

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74340

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000248 AC: 3

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	0.29
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.5
DANN	Benign	0.58
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.88
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.064
Sift	Benign	0.36	T
Sift4G	Benign	0.21	T
Polyphen		0.22	B
Vest4		0.37
MutPred		0.47		Gain of disorder (P = 0.003)
MVP		0.055
MPC		0.29
ClinPred		0.054	T
GERP RS		2.9
Varity_R		0.11
gMVP		0.34
Mutation Taster		=86/14	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: rs764964844; hg19: chr17-19582180;