chr17-82237290-T-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_004207.4(SLC16A3):c.520T>G(p.Tyr174Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SLC16A3
NM_004207.4 missense
NM_004207.4 missense
Scores
8
2
4
Clinical Significance
Conservation
PhyloP100: 7.91
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.974
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC16A3 | NM_004207.4 | c.520T>G | p.Tyr174Asp | missense_variant | 4/5 | ENST00000582743.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC16A3 | ENST00000582743.6 | c.520T>G | p.Tyr174Asp | missense_variant | 4/5 | 1 | NM_004207.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1409738Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 696676
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1409738
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
696676
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 14, 2023 | The c.520T>G (p.Y174D) alteration is located in exon 4 (coding exon 3) of the SLC16A3 gene. This alteration results from a T to G substitution at nucleotide position 520, causing the tyrosine (Y) at amino acid position 174 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Benign
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;D;D;.;T;D;D;.;.;.;D;.;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
.;D;.;D;.;.;.;D;D;D;.;D;.
Vest4
0.89, 0.89, 0.85
MutPred
Loss of methylation at R177 (P = 0.0467);Loss of methylation at R177 (P = 0.0467);Loss of methylation at R177 (P = 0.0467);Loss of methylation at R177 (P = 0.0467);.;.;Loss of methylation at R177 (P = 0.0467);Loss of methylation at R177 (P = 0.0467);Loss of methylation at R177 (P = 0.0467);Loss of methylation at R177 (P = 0.0467);Loss of methylation at R177 (P = 0.0467);Loss of methylation at R177 (P = 0.0467);.;
MVP
MPC
1.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at