17-82237287-C-T

Variant names:

• chr17-82237287-C-T
• rs940545976
• NM_004207.4:c.517C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004207.4(SLC16A3):​c.517C>T​(p.Arg173Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,562,838 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SLC16A3 NM_004207.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.642

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29799396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A3	NM_004207.4	c.517C>T	p.Arg173Cys	missense_variant	Exon 4 of 5	ENST00000582743.6	NP_004198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A3	ENST00000582743.6	c.517C>T	p.Arg173Cys	missense_variant	Exon 4 of 5	1	NM_004207.4	ENSP00000462405.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000599 AC: 1 AN: 167044 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 90636

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000421

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000142 AC: 20 AN: 1410642 Hom.: 0 Cov.: 31 AF XY: 0.0000186 AC XY: 13 AN XY: 697198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000373

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000147

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.517C>T (p.R173C) alteration is located in exon 4 (coding exon 3) of the SLC16A3 gene. This alteration results from a C to T substitution at nucleotide position 517, causing the arginine (R) at amino acid position 173 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.57	.;D;.;D;D;.;.;D;D;D;.;D;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.92	D;T;D;.;D;D;D;.;.;.;D;.;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.30	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.0	.;L;.;L;.;.;.;L;L;L;.;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.8	.;D;.;.;.;.;.;D;.;.;.;.;.
REVEL	Benign	0.14
Sift	Benign	0.065	.;T;.;.;.;.;.;T;.;.;.;.;.
Sift4G	Benign	0.062	T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.96	.;D;.;D;.;.;.;D;D;D;.;D;.
Vest4		0.18, 0.17, 0.18, 0.15
MutPred		0.40		Loss of methylation at R177 (P = 0.1265);Loss of methylation at R177 (P = 0.1265);Loss of methylation at R177 (P = 0.1265);Loss of methylation at R177 (P = 0.1265);.;.;Loss of methylation at R177 (P = 0.1265);Loss of methylation at R177 (P = 0.1265);Loss of methylation at R177 (P = 0.1265);Loss of methylation at R177 (P = 0.1265);Loss of methylation at R177 (P = 0.1265);Loss of methylation at R177 (P = 0.1265);.;
MVP		0.49
MPC		0.87
ClinPred		0.74	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.085
gMVP		0.29

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: rs940545976; hg19: chr17-80195163;