NM_001099646.3:c.1177G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.54

Publications

23 publications found

Variant links:

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 links:

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

ALDH3A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar as Benign. Clinvar id is 3387889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-19681658-C-T is described in CliVar 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. 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC47A2	NM_001099646.3 link	c.1177G>A	p.Gly393Arg	missense_variant	Exon 14 of 17	ENST00000433844.4	NP_001093116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC47A2	ENST00000433844.4 link	c.1177G>A	p.Gly393Arg	missense_variant	Exon 14 of 17	5	NM_001099646.3	ENSP00000391848.3		Q86VL8-3C9JAE6

Frequencies

GnomAD3 genomes

AF:

0.00456

AC:

694

AN:

152152

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.00669

AC XY:

4860

AN XY:

726318

show subpopulations

African (AFR)

AF:

0.00108

AC:

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:

AN:

39680

South Asian (SAS)

AF:

0.0144

AC:

1243

AN:

86118

European-Finnish (FIN)

AF:

0.000656

AC:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

488

976

1464

1952

2440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00454

AC:

691

AN:

152270

Hom.:

Cov.:

AF XY:

0.00465

AC XY:

346

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41560

American (AMR)

AF:

0.00542

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0127

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00666

AC:

453

AN:

68004

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00639

Hom.:

Bravo

AF:

0.00459

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00674

AC:

ExAC

AF:

0.00607

AC:

737

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.00866

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC47A2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;.

Eigen

Benign

-0.094

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.10

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Pathogenic

4.2

H;.

PhyloP100

1.5

PrimateAI

Benign

0.32

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

GERP RS

1.3

Varity_R

0.58

gMVP

0.81

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over