1-112913924-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003051.4(SLC16A1):c.1470T>A(p.Asp490Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,613,802 control chromosomes in the GnomAD database, including 278,152 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33924 hom., cov: 32)

Exomes 𝑓: 0.57 ( 244228 hom. )

Consequence

SLC16A1
NM_003051.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.105

Publications

144 publications found

Variant links:

Genes affected

SLC16A1 (HGNC:10922): (solute carrier family 16 member 1) The protein encoded by this gene is a proton-linked monocarboxylate transporter that catalyzes the movement of many monocarboxylates, such as lactate and pyruvate, across the plasma membrane. Mutations in this gene are associated with erythrocyte lactate transporter defect. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2009]

SLC16A1 links:

SLC16A1-AS1 (HGNC:49445): (SLC16A1 antisense RNA 1)

SLC16A1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.3899806E-7).

BP6

Variant 1-112913924-A-T is Benign according to our data. Variant chr1-112913924-A-T is described in ClinVar as Benign. ClinVar VariationId is 130315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SLC16A1	NM_003051.4 link	c.1470T>A	p.Asp490Glu	missense_variant	Exon 5 of 5	ENST00000369626.8	NP_003042.3
SLC16A1	NM_001166496.2 link	c.1470T>A	p.Asp490Glu	missense_variant	Exon 5 of 5		NP_001159968.1
SLC16A1	XM_047428789.1 link	c.1470T>A	p.Asp490Glu	missense_variant	Exon 5 of 5		XP_047284745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A1	ENST00000369626.8 link	c.1470T>A	p.Asp490Glu	missense_variant	Exon 5 of 5	1	NM_003051.4	ENSP00000358640.4

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99407

AN:

151898

Hom.:

33864

Cov.:

show subpopulations

Gnomad AFR

AF:

0.856

Gnomad AMI

AF:

0.568

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.586

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.645

GnomAD2 exomes

AF:

0.592

AC:

148782

AN:

251466

AF XY:

0.587

show subpopulations

Gnomad AFR exome

AF:

0.862

Gnomad AMR exome

AF:

0.522

Gnomad ASJ exome

AF:

0.631

Gnomad EAS exome

AF:

0.670

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.592

GnomAD4 exome

AF:

0.575

AC:

840521

AN:

1461786

Hom.:

244228

Cov.:

AF XY:

0.574

AC XY:

417382

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.866

AC:

29006

AN:

33478

American (AMR)

AF:

0.529

AC:

23658

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

16439

AN:

26134

East Asian (EAS)

AF:

0.665

AC:

26399

AN:

39696

South Asian (SAS)

AF:

0.547

AC:

47197

AN:

86256

European-Finnish (FIN)

AF:

0.577

AC:

30795

AN:

53416

Middle Eastern (MID)

AF:

0.644

AC:

3713

AN:

5766

European-Non Finnish (NFE)

AF:

0.564

AC:

627570

AN:

1111922

Other (OTH)

AF:

0.592

AC:

35744

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

21773

43546

65319

87092

108865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17536

35072

52608

70144

87680

<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:

0.655

AC:

99530

AN:

152016

Hom.:

33924

Cov.:

AF XY:

0.652

AC XY:

48465

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.856

AC:

35546

AN:

41502

American (AMR)

AF:

0.565

AC:

8630

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

2202

AN:

3466

East Asian (EAS)

AF:

0.661

AC:

3407

AN:

5158

South Asian (SAS)

AF:

0.567

AC:

2727

AN:

4812

European-Finnish (FIN)

AF:

0.586

AC:

6181

AN:

10546

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.570

AC:

38749

AN:

67940

Other (OTH)

AF:

0.649

AC:

1374

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1671

3342

5013

6684

8355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<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:

0.589

Hom.:

20138

Bravo

AF:

0.662

TwinsUK

AF:

0.565

AC:

2096

ALSPAC

AF:

0.568

AC:

2189

ESP6500AA

AF:

0.845

AC:

3721

ESP6500EA

AF:

0.575

AC:

4944

ExAC

AF:

0.597

AC:

72494

Asia WGS

AF:

0.635

AC:

2209

AN:

3478

EpiCase

AF:

0.575

EpiControl

AF:

0.581

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 25, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26595136) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Exercise-induced hyperinsulinism

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ketoacidosis due to monocarboxylate transporter-1 deficiency

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Metabolic myopathy due to lactate transporter defect

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.3

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.071

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0076

MetaRNN

Benign

8.4e-7

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.34

N;N

PhyloP100

-0.10

PrimateAI

Benign

0.30

PROVEAN

Benign

0.49

N;N

REVEL

Benign

0.035

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.066

MutPred

0.14

Gain of glycosylation at P493 (P = 0.16);Gain of glycosylation at P493 (P = 0.16);

MPC

0.31

ClinPred

0.0057

GERP RS

2.7

Varity_R

0.051

gMVP

0.094

Mutation Taster

=98/2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over