dbSNP rs1048046: SLC67A1:p.Ala6Thr (chr11-2903361-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002555.6(SLC67A1):c.16G>A(p.Ala6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,612,492 control chromosomes in the GnomAD database, including 27,823 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3441 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24382 hom. )

Consequence

SLC67A1
NM_002555.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.474

Publications

30 publications found

Variant links:

Genes affected

SLC67A1 (HGNC:10964): (solute carrier family 22 member 18) This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2015]

SLC67A1 links:

SLC22A18AS (HGNC:10965): (SLC22A18 antisense RNA)

SLC22A18AS 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=0.015569568).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC67A1	NM_002555.6 link	c.16G>A	p.Ala6Thr	missense_variant	Exon 2 of 11	ENST00000649076.2	NP_002546.3	Q96BI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A18	ENST00000649076.2 link	c.16G>A	p.Ala6Thr	missense_variant	Exon 2 of 11		NM_002555.6	ENSP00000497561.1		Q96BI1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30178

AN:

151926

Hom.:

3432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.00290

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.177

GnomAD2 exomes

AF:

0.172

AC:

42833

AN:

249634

AF XY:

0.173

show subpopulations

Gnomad AFR exome

AF:

0.276

Gnomad AMR exome

AF:

0.0859

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.00152

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.176

AC:

256728

AN:

1460448

Hom.:

24382

Cov.:

AF XY:

0.177

AC XY:

128275

AN XY:

726522

show subpopulations

African (AFR)

AF:

0.280

AC:

9360

AN:

33472

American (AMR)

AF:

0.0920

AC:

4112

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

4314

AN:

26124

East Asian (EAS)

AF:

0.00123

AC:

AN:

39700

South Asian (SAS)

AF:

0.184

AC:

15902

AN:

86250

European-Finnish (FIN)

AF:

0.302

AC:

15819

AN:

52354

Middle Eastern (MID)

AF:

0.150

AC:

866

AN:

5764

European-Non Finnish (NFE)

AF:

0.176

AC:

195722

AN:

1111704

Other (OTH)

AF:

0.175

AC:

10584

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

11114

22228

33343

44457

55571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6774

13548

20322

27096

33870

<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:

0.199

AC:

30213

AN:

152044

Hom.:

3441

Cov.:

AF XY:

0.201

AC XY:

14974

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.265

AC:

10969

AN:

41446

American (AMR)

AF:

0.120

AC:

1838

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

553

AN:

3470

East Asian (EAS)

AF:

0.00291

AC:

AN:

5158

South Asian (SAS)

AF:

0.183

AC:

883

AN:

4826

European-Finnish (FIN)

AF:

0.307

AC:

3257

AN:

10592

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12125

AN:

67930

Other (OTH)

AF:

0.175

AC:

371

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1148

2296

3445

4593

5741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.180

Hom.:

3538

Bravo

AF:

0.188

TwinsUK

AF:

0.170

AC:

631

ALSPAC

AF:

0.181

AC:

699

ESP6500AA

AF:

0.264

AC:

1163

ESP6500EA

AF:

0.180

AC:

1545

ExAC

AF:

0.176

AC:

21406

Asia WGS

AF:

0.113

AC:

395

AN:

3478

EpiCase

AF:

0.174

EpiControl

AF:

0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00063

T;T;T;.;T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.52

.;.;.;T;T;T

MetaRNN

Benign

0.016

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;M;.;M;.

PhyloP100

0.47

PrimateAI

Benign

0.45

PROVEAN

Benign

0.020

N;N;.;N;N;N

REVEL

Benign

0.048

Sift

Benign

0.15

T;T;.;D;T;T

Sift4G

Pathogenic

0.0

D;D;.;D;D;D

Polyphen

0.028

B;B;B;B;B;.

Vest4

0.032

MPC

0.17

ClinPred

0.0056

GERP RS

0.67

PromoterAI

0.0048

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.39

Mutation Taster

=99/1

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