17-82236052-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.84

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 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 GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC16A3	NM_004207.4	c.44C>T	p.Ala15Val	missense_variant	2/5	ENST00000582743.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A3	ENST00000582743.6	c.44C>T	p.Ala15Val	missense_variant	2/5	1	NM_004207.4	P1

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 388 AN: 152238 Hom.: 3 Cov.: 33

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.: 19 AF XY: 0.00544 AC XY: 736 AN XY: 135256

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.: 58 Cov.: 31 AF XY: 0.00315 AC XY: 2291 AN XY: 726458

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.: 3 Cov.: 33 AF XY: 0.00311 AC XY: 232 AN XY: 74504

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.: 0

Bravo AF: 0.00186

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00505 AC: 612

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.21
Cadd	Pathogenic	26
Dann	Uncertain	0.99
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
MutationTaster	Benign	1.0	D;D;D;D
ClinPred		0.024	T
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

Other links and lift over

dbSNP: rs144588703; hg19: chr17-80193928;