NM_001099646.3:c.1177G>A

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

4
5
9

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]
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

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
SLC47A2NM_001099646.3 linkc.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
SLC47A2ENST00000433844.4 linkc.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.:
5
Cov.:
32
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.:
48
Cov.:
31
AF XY:
0.00669
AC XY:
4860
AN XY:
726318
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
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
0
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.:
5
Cov.:
32
AF XY:
0.00465
AC XY:
346
AN XY:
74464
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
38
75
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
0
20
40
60
80
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.:
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

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
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;.
PhyloP100
1.5
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
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

Publications

Other links and lift over

dbSNP: rs34399035; hg19: chr17-19584971; API