rs34416664

Positions:

• chr17-19681439-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001099646.3(SLC47A2):​c.1320C>G​(p.Ala440=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,613,902 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (7 hom., cov: 32)
  • Exomes 𝑓: 0.010 (101 hom.)
• Consequence: SLC47A2 NM_001099646.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.815

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 17-19681439-G-C is Benign according to our data. Variant chr17-19681439-G-C is described in ClinVar as [Benign]. Clinvar id is 3257582.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.815 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC47A2	NM_001099646.3	c.1320C>G	p.Ala440=	synonymous_variant	15/17	ENST00000433844.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC47A2	ENST00000433844.4	c.1320C>G	p.Ala440=	synonymous_variant	15/17	5	NM_001099646.3	P1

Frequencies

GnomAD3 genomes AF: 0.00793 AC: 1207 AN: 152152 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00809 AC: 2028 AN: 250656 Hom.: 15 AF XY: 0.00848 AC XY: 1149 AN XY: 135484

Gnomad AFR exome AF: 0.00241

Gnomad AMR exome AF: 0.00499

Gnomad ASJ exome AF: 0.00716

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00557

Gnomad FIN exome AF: 0.0111

Gnomad NFE exome AF: 0.0112

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.0103 AC: 15060 AN: 1461632 Hom.: 101 Cov.: 31 AF XY: 0.0103 AC XY: 7521 AN XY: 727088

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00495

Gnomad4 ASJ exome AF: 0.00762

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00582

Gnomad4 FIN exome AF: 0.0106

Gnomad4 NFE exome AF: 0.0117

Gnomad4 OTH exome AF: 0.00808

GnomAD4 genome AF: 0.00794 AC: 1209 AN: 152270 Hom.: 7 Cov.: 32 AF XY: 0.00792 AC XY: 590 AN XY: 74474

Gnomad4 AFR AF: 0.00253

Gnomad4 AMR AF: 0.00725

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.0115

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00938 Hom.: 4

Bravo AF: 0.00759

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0107

EpiControl AF: 0.0115

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

SLC47A2: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.7
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs34416664; hg19: chr17-19584752;