rs60425436

Variant names:

• chr17-19679864-A-G
• rs60425436
• NM_001099646.3:c.1480+88T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001099646.3(SLC47A2):​c.1480+88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,315,464 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (39 hom.)
• Consequence: SLC47A2 NM_001099646.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 2 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: G2P, Myriad Women’s Health, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0142 (2163/152154) while in subpopulation AFR AF = 0.0495 (2053/41476). AF 95% confidence interval is 0.0477. There are 53 homozygotes in GnomAd4. There are 1038 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC47A2	NM_001099646.3	c.1480+88T>C		intron_variant	Intron 16 of 16	ENST00000433844.4	NP_001093116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC47A2	ENST00000433844.4	c.1480+88T>C		intron_variant	Intron 16 of 16	5	NM_001099646.3	ENSP00000391848.3

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2162 AN: 152036 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00137 AC: 1599 AN: 1163310 Hom.: 39 AF XY: 0.00117 AC XY: 673 AN XY: 575926

African (AFR) AF: 0.0510 AC: 1321 AN: 25890

American (AMR) AF: 0.00250 AC: 66 AN: 26438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19206

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35790

South Asian (SAS) AF: 0.0000929 AC: 6 AN: 64582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48282

Middle Eastern (MID) AF: 0.00139 AC: 7 AN: 5050

European-Non Finnish (NFE) AF: 0.0000428 AC: 38 AN: 888676

Other (OTH) AF: 0.00324 AC: 160 AN: 49396

GnomAD4 genome AF: 0.0142 AC: 2163 AN: 152154 Hom.: 53 Cov.: 32 AF XY: 0.0140 AC XY: 1038 AN XY: 74390

African (AFR) AF: 0.0495 AC: 2053 AN: 41476

American (AMR) AF: 0.00497 AC: 76 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

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

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68018

Other (OTH) AF: 0.0109 AC: 23 AN: 2104

Alfa AF: 0.0173 Hom.: 8

Bravo AF: 0.0157

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.73
PhyloP100		-1.6
Mutation Taster		=100/0	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: rs60425436; hg19: chr17-19583177;