dbSNP rs77474263: SLC47A1:p.Leu125Phe (chr17-19548051-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018242.3(SLC47A1):c.373C>T(p.Leu125Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,614,144 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0082 ( 59 hom., cov: 31)

Exomes 𝑓: 0.0049 ( 464 hom. )

Consequence

SLC47A1
NM_018242.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.71

Publications

13 publications found

Variant links:

Genes affected

SLC47A1 (HGNC:25588): (solute carrier family 47 member 1) This gene is located within the Smith-Magenis syndrome region on chromosome 17. It encodes a protein of unknown function. [provided by RefSeq, Jul 2008]

SLC47A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039165616).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC47A1	NM_018242.3 link	c.373C>T	p.Leu125Phe	missense_variant	Exon 4 of 17	ENST00000270570.8	NP_060712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC47A1	ENST00000270570.8 link	c.373C>T	p.Leu125Phe	missense_variant	Exon 4 of 17	1	NM_018242.3	ENSP00000270570.4

Frequencies

GnomAD3 genomes

AF:

0.00818

AC:

1245

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00814

GnomAD2 exomes

AF:

0.0209

AC:

5259

AN:

251360

AF XY:

0.0157

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00516

Gnomad FIN exome

AF:

0.00486

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.00487

AC:

7119

AN:

1461832

Hom.:

464

Cov.:

AF XY:

0.00417

AC XY:

3030

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000836

AC:

AN:

33478

American (AMR)

AF:

0.130

AC:

5834

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

286

AN:

26136

East Asian (EAS)

AF:

0.00731

AC:

290

AN:

39698

South Asian (SAS)

AF:

0.000742

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00480

AC:

256

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000107

AC:

119

AN:

1112008

Other (OTH)

AF:

0.00401

AC:

242

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

356

712

1069

1425

1781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.00820

AC:

1249

AN:

152312

Hom.:

Cov.:

AF XY:

0.00990

AC XY:

737

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.000745

AC:

AN:

41584

American (AMR)

AF:

0.0698

AC:

1067

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3470

East Asian (EAS)

AF:

0.00347

AC:

AN:

5182

South Asian (SAS)

AF:

0.00145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00471

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68026

Other (OTH)

AF:

0.00806

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

120

181

241

301

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:

0.00361

Hom.:

Bravo

AF:

0.0132

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.0157

AC:

1901

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

T;T;.;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

D;D;D;D

MetaRNN

Benign

0.0039

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.0

.;M;.;M

PhyloP100

2.7

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.9

D;D;.;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0030

D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.39

MPC

0.72

ClinPred

0.022

GERP RS

4.0

Varity_R

0.57

gMVP

0.42

Mutation Taster

=281/19

polymorphism (auto)

(source)

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

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

Computational scores

Splicing

Publications

Other links and lift over