1-112913924-A-T

Position:

chr1-112913924-A-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 130315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-112913924-A-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
SLC16A1	NM_003051.4 linkuse as main transcript	c.1470T>A	p.Asp490Glu	missense_variant	5/5	ENST00000369626.8	NP_003042.3	P53985-1A0A024R0H1
SLC16A1	NM_001166496.2 linkuse as main transcript	c.1470T>A	p.Asp490Glu	missense_variant	5/5		NP_001159968.1	P53985-1A0A024R0H1B4DKS0
SLC16A1	XM_047428789.1 linkuse as main transcript	c.1470T>A	p.Asp490Glu	missense_variant	5/5		XP_047284745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A1	ENST00000369626.8 linkuse as main transcript	c.1470T>A	p.Asp490Glu	missense_variant	5/5	1	NM_003051.4	ENSP00000358640.4		P53985-1

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

GnomAD3 exomes

AF:

0.592

AC:

148782

AN:

251466

Hom.:

45046

AF XY:

0.587

AC XY:

79718

AN XY:

135904

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 SAS exome

AF:

0.548

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

Gnomad4 AFR exome

AF:

0.866

Gnomad4 AMR exome

AF:

0.529

Gnomad4 ASJ exome

AF:

0.629

Gnomad4 EAS exome

AF:

0.665

Gnomad4 SAS exome

AF:

0.547

Gnomad4 FIN exome

AF:

0.577

Gnomad4 NFE exome

AF:

0.564

Gnomad4 OTH exome

AF:

0.592

GnomAD4 genome

AF:

0.655

AC:

99530

AN:

152016

Hom.:

33924

Cov.:

AF XY:

0.652

AC XY:

48465

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.856

Gnomad4 AMR

AF:

0.565

Gnomad4 ASJ

AF:

0.635

Gnomad4 EAS

AF:

0.661

Gnomad4 SAS

AF:

0.567

Gnomad4 FIN

AF:

0.586

Gnomad4 NFE

AF:

0.570

Gnomad4 OTH

AF:

0.649

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 25, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 26595136) -

Exercise-induced hyperinsulinism

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

Ketoacidosis due to monocarboxylate transporter-1 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Metabolic myopathy due to lactate transporter defect

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over