17-19681658-C-T

Variant names:

• chr17-19681658-C-T
• rs34399035
• NM_001099646.3:c.1177G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 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 GnomAdExome4. There are 4860 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A2	NM_001099646.3	MANE Select	c.1177G>A	p.Gly393Arg	missense	Exon 14 of 17	NP_001093116.1	Q86VL8-3
	SLC47A2	NM_152908.5		c.1285G>A	p.Gly429Arg	missense	Exon 14 of 17	NP_690872.2
	SLC47A2	NM_001256663.3		c.1219G>A	p.Gly407Arg	missense	Exon 15 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.1177G>A	p.Gly393Arg	missense	Exon 14 of 17	ENSP00000391848.3	Q86VL8-3
	SLC47A2	ENST00000325411.9	TSL:1	c.1285G>A	p.Gly429Arg	missense	Exon 14 of 17	ENSP00000326671.5	Q86VL8-1
	SLC47A2	ENST00000350657.9	TSL:1	c.1219G>A	p.Gly407Arg	missense	Exon 15 of 18	ENSP00000338084.6	Q86VL8-4

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

GnomAD2 exomes AF: 0.00600 AC: 1499 AN: 249926 AF XY: 0.00676

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 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

African (AFR) AF: 0.00108 AC: 36 AN: 33452

American (AMR) AF: 0.00383 AC: 171 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00553 AC: 144 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0144 AC: 1243 AN: 86118

European-Finnish (FIN) AF: 0.000656 AC: 35 AN: 53376

Middle Eastern (MID) AF: 0.0283 AC: 163 AN: 5768

European-Non Finnish (NFE) AF: 0.00631 AC: 7009 AN: 1110930

Other (OTH) AF: 0.00668 AC: 403 AN: 60342

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

African (AFR) AF: 0.000962 AC: 40 AN: 41560

American (AMR) AF: 0.00542 AC: 83 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0127 AC: 61 AN: 4818

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00666 AC: 453 AN: 68004

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00639 Hom.: 23

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

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
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
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	4.2	H
PhyloP100		1.5
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs34399035; hg19: chr17-19584971;