Genetic Variant SLC16A3:p.Ala15Val (chr17-82236052-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004207.4(SLC16A3):c.44C>T(p.Ala15Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,612,684 control chromosomes in the GnomAD database, including 61 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 58 hom. )

Consequence

SLC16A3
NM_004207.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.84

Variant links:

Genes affected

SLC16A3 (HGNC:10924): (solute carrier family 16 member 3) Lactic acid and pyruvate transport across plasma membranes is catalyzed by members of the proton-linked monocarboxylate transporter (MCT) family, which has been designated solute carrier family-16. Each MCT appears to have slightly different substrate and inhibitor specificities and transport kinetics, which are related to the metabolic requirements of the tissues in which it is found. The MCTs, which include MCT1 (SLC16A1; MIM 600682) and MCT2 (SLC16A7; MIM 603654), are characterized by 12 predicted transmembrane domains (Price et al., 1998 [PubMed 9425115]).[supplied by OMIM, Mar 2008]

SLC16A3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 17-82236052-C-T is Benign according to our data. Variant chr17-82236052-C-T is described in ClinVar as [Benign]. Clinvar id is 725993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00253 (385/152356) while in subpopulation SAS AF= 0.0325 (157/4832). AF 95% confidence interval is 0.0283. There are 3 homozygotes in gnomad4. There are 232 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A3	NM_004207.4 link	c.44C>T	p.Ala15Val	missense_variant	Exon 2 of 5	ENST00000582743.6	NP_004198.1	O15427A0A024R8U1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A3	ENST00000582743.6 link	c.44C>T	p.Ala15Val	missense_variant	Exon 2 of 5	1	NM_004207.4	ENSP00000462405.1		O15427

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

388

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.0327

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00442

AC:

1101

AN:

248934

Hom.:

AF XY:

0.00544

AC XY:

736

AN XY:

135256

show subpopulations

Gnomad AFR exome

AF:

0.00393

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.00747

Gnomad SAS exome

AF:

0.0265

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000420

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00237

AC:

3461

AN:

1460328

Hom.:

Cov.:

AF XY:

0.00315

AC XY:

2291

AN XY:

726458

show subpopulations

Gnomad4 AFR exome

AF:

0.00448

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.0124

Gnomad4 SAS exome

AF:

0.0265

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.00351

GnomAD4 genome

AF:

0.00253

AC:

385

AN:

152356

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

232

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00322

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0112

Gnomad4 SAS

AF:

0.0325

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.00186

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00505

AC:

612

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.97

ClinPred

0.024

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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