rs34416664

Variant names:

• chr17-19681439-G-C
• rs34416664
• NM_001099646.3:c.1320C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001099646.3(SLC47A2):​c.1320C>G​(p.Ala440Ala) 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
• Publications: 7 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 -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 VariationId 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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A2	NM_001099646.3	MANE Select	c.1320C>G	p.Ala440Ala	synonymous	Exon 15 of 17	NP_001093116.1
	SLC47A2	NM_152908.5		c.1428C>G	p.Ala476Ala	synonymous	Exon 15 of 17	NP_690872.2
	SLC47A2	NM_001256663.3		c.1362C>G	p.Ala454Ala	synonymous	Exon 16 of 18	NP_001243592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A2	ENST00000433844.4	TSL:5 MANE Select	c.1320C>G	p.Ala440Ala	synonymous	Exon 15 of 17	ENSP00000391848.3
	SLC47A2	ENST00000325411.9	TSL:1	c.1428C>G	p.Ala476Ala	synonymous	Exon 15 of 17	ENSP00000326671.5
	SLC47A2	ENST00000350657.9	TSL:1	c.1362C>G	p.Ala454Ala	synonymous	Exon 16 of 18	ENSP00000338084.6

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

GnomAD2 exomes AF: 0.00809 AC: 2028 AN: 250656 AF XY: 0.00848

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 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

African (AFR) AF: 0.00152 AC: 51 AN: 33478

American (AMR) AF: 0.00495 AC: 221 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00762 AC: 199 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00582 AC: 502 AN: 86214

European-Finnish (FIN) AF: 0.0106 AC: 565 AN: 53404

Middle Eastern (MID) AF: 0.0123 AC: 71 AN: 5768

European-Non Finnish (NFE) AF: 0.0117 AC: 12962 AN: 1111900

Other (OTH) AF: 0.00808 AC: 488 AN: 60392

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

African (AFR) AF: 0.00253 AC: 105 AN: 41558

American (AMR) AF: 0.00725 AC: 111 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4812

European-Finnish (FIN) AF: 0.0123 AC: 131 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0115 AC: 781 AN: 68010

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.7
DANN	Benign	0.73
PhyloP100		0.81
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: rs34416664; hg19: chr17-19584752;