17-82237287-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.642
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
SLC16A3NM_004207.4 linkc.517C>T p.Arg173Cys missense_variant Exon 4 of 5 ENST00000582743.6 NP_004198.1 O15427A0A024R8U1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC16A3ENST00000582743.6 linkc.517C>T p.Arg173Cys missense_variant Exon 4 of 5 1 NM_004207.4 ENSP00000462405.1 O15427

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

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

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

Other links and lift over

dbSNP: rs940545976; hg19: chr17-80195163; API