rs140728650

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting

The NM_003051.4(SLC16A1):c.1063G>A(p.Gly355Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000558 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

SLC16A1
NM_003051.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 6.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38635474).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000322 (49/152252) while in subpopulation AFR AF= 0.00116 (48/41540). AF 95% confidence interval is 0.000895. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC16A1	NM_003051.4 linkuse as main transcript	c.1063G>A	p.Gly355Arg	missense_variant	4/5	ENST00000369626.8
SLC16A1	NM_001166496.2 linkuse as main transcript	c.1063G>A	p.Gly355Arg	missense_variant	4/5
SLC16A1	XM_047428789.1 linkuse as main transcript	c.1063G>A	p.Gly355Arg	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A1	ENST00000369626.8 linkuse as main transcript	c.1063G>A	p.Gly355Arg	missense_variant	4/5	1	NM_003051.4	P1	P53985-1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

251450

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000322

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000793

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 24, 2015

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 30, 2023

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 355 of the SLC16A1 protein (p.Gly355Arg). This variant is present in population databases (rs140728650, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with SLC16A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 212183). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

SLC16A1-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2023

The SLC16A1 c.1063G>A variant is predicted to result in the amino acid substitution p.Gly355Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.088% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-113459965-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Uncertain

0.12

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;D;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.041

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Pathogenic

3.5

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.2

D;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.018

D;D;D

Sift4G

Uncertain

0.045

D;D;.

Polyphen

0.94

P;P;.

Vest4

0.87

MutPred

0.77

Gain of methylation at G355 (P = 0.0062);Gain of methylation at G355 (P = 0.0062);Gain of methylation at G355 (P = 0.0062);

MVP

0.70

MPC

0.92

ClinPred

0.96

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.92

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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