dbSNP rs77630697: SLC47A1:p.Gly64Asp (chr17-19542448-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BP4_StrongBS2

The NM_018242.3(SLC47A1):c.191G>A(p.Gly64Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000246 in 1,612,528 control chromosomes in the GnomAD database, including 7 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 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 7 hom. )

Consequence

SLC47A1
NM_018242.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.81

Publications

19 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 -7 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 11: AlphaMissense, BayesDel_noAF, Cadd, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL, REVEL [when max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.043067187).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC47A1	NM_018242.3 link	c.191G>A	p.Gly64Asp	missense_variant	Exon 2 of 17	ENST00000270570.8	NP_060712.2	Q96FL8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC47A1	ENST00000270570.8 link	c.191G>A	p.Gly64Asp	missense_variant	Exon 2 of 17	1	NM_018242.3	ENSP00000270570.4		Q96FL8-1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00734

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000508

AC:

127

AN:

249968

AF XY:

0.000421

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00686

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000246

AC:

359

AN:

1460266

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

154

AN XY:

726502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.0000226

AC:

AN:

44334

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00819

AC:

324

AN:

39570

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111442

Other (OTH)

AF:

0.000498

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000250

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00736

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000295

Hom.:

Bravo

AF:

0.000332

ExAC

AF:

0.000544

AC:

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;D;.;.

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.98

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.073

MetaRNN

Benign

0.043

T;T;T;T

MetaSVM

Uncertain

0.36

MutationAssessor

Pathogenic

4.1

.;H;.;H

PhyloP100

8.8

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-6.6

D;D;.;D

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

D;D;.;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.94

MVP

0.60

MPC

0.79

ClinPred

0.30

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.92

Mutation Taster

=197/103

polymorphism

(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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rs77630697

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