Genetic Variant NM_018242.3:c.373C>T (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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018242.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A1	NM_018242.3	MANE Select	c.373C>T	p.Leu125Phe	missense	Exon 4 of 17	NP_060712.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC47A1	ENST00000270570.8	TSL:1 MANE Select	c.373C>T	p.Leu125Phe	missense	Exon 4 of 17	ENSP00000270570.4
SLC47A1	ENST00000395585.5	TSL:1	c.373C>T	p.Leu125Phe	missense	Exon 4 of 19	ENSP00000378951.1
SLC47A1	ENST00000575023.5	TSL:1	c.373C>T	p.Leu125Phe	missense	Exon 4 of 7	ENSP00000460164.1

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 v4.9

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

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.0

PhyloP100

2.7

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.44

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

1.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over