17-19681658-C-T

Position:

• chr17-19681658-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001099646.3(SLC47A2):​c.1177G>A​(p.Gly393Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00614 in 1,612,630 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (48 hom.)
• Consequence: SLC47A2 NM_001099646.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54

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]

SLC47A2 (HGNC:):

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024230838).
• BP6: Variant 17-19681658-C-T is Benign according to our data. Variant chr17-19681658-C-T is described in ClinVar as [Benign]. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0063 (9204/1460360) while in subpopulation MID AF= 0.0283 (163/5768). AF 95% confidence interval is 0.0247. There are 48 homozygotes in gnomad4_exome. There are 4860 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC47A2	NM_001099646.3	c.1177G>A	p.Gly393Arg	missense_variant	14/17	ENST00000433844.4	NP_001093116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC47A2	ENST00000433844.4	c.1177G>A	p.Gly393Arg	missense_variant	14/17	5	NM_001099646.3	ENSP00000391848.3

Frequencies

GnomAD3 genomes AF: 0.00456 AC: 694 AN: 152152 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00666

Gnomad OTH AF: 0.00716

GnomAD3 exomes AF: 0.00600 AC: 1499 AN: 249926 Hom.: 9 AF XY: 0.00676 AC XY: 913 AN XY: 135022

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.00646

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0153

Gnomad FIN exome AF: 0.000744

Gnomad NFE exome AF: 0.00684

Gnomad OTH exome AF: 0.00655

GnomAD4 exome AF: 0.00630 AC: 9204 AN: 1460360 Hom.: 48 Cov.: 31 AF XY: 0.00669 AC XY: 4860 AN XY: 726318

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00383

Gnomad4 ASJ exome AF: 0.00553

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0144

Gnomad4 FIN exome AF: 0.000656

Gnomad4 NFE exome AF: 0.00631

Gnomad4 OTH exome AF: 0.00668

GnomAD4 genome AF: 0.00454 AC: 691 AN: 152270 Hom.: 5 Cov.: 32 AF XY: 0.00465 AC XY: 346 AN XY: 74464

Gnomad4 AFR AF: 0.000962

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0127

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00690 Hom.: 16

Bravo AF: 0.00459

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00674 AC: 58

ExAC AF: 0.00607 AC: 737

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00916

EpiControl AF: 0.00866

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

Sep 01, 2024

SLC47A2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.
Eigen	Benign	-0.094
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.93	D;D
MetaRNN	Benign	0.024	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	4.2	H;.
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-7.3	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.85
MutPred		0.33		Loss of catalytic residue at V430 (P = 0.0432);.;
MVP		0.18
MPC		0.57
ClinPred		0.099	T
GERP RS		1.3
Varity_R		0.58
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34399035; hg19: chr17-19584971;