chr17-82236756-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004207.4(SLC16A3):c.251G>A(p.Arg84His) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,607,984 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
SLC16A3
NM_004207.4 missense
NM_004207.4 missense
Scores
3
7
4
Clinical Significance
Conservation
PhyloP100: 6.79
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]
MIR6787 (HGNC:50209): (microRNA 6787) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC16A3 | NM_004207.4 | c.251G>A | p.Arg84His | missense_variant | 3/5 | ENST00000582743.6 | |
MIR6787 | NR_106845.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC16A3 | ENST00000582743.6 | c.251G>A | p.Arg84His | missense_variant | 3/5 | 1 | NM_004207.4 | P1 | |
MIR6787 | ENST00000616675.1 | downstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000206 AC: 5AN: 242348Hom.: 0 AF XY: 0.00000759 AC XY: 1AN XY: 131816
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GnomAD4 exome AF: 0.0000124 AC: 18AN: 1455778Hom.: 0 Cov.: 32 AF XY: 0.00000828 AC XY: 6AN XY: 724520
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358
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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 | Dec 21, 2023 | The c.251G>A (p.R84H) alteration is located in exon 3 (coding exon 2) of the SLC16A3 gene. This alteration results from a G to A substitution at nucleotide position 251, causing the arginine (R) at amino acid position 84 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.;D;D;.;.;D;.;D;D;.
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D;D;D;D;T;D;D;D;T;D;D;T;D
Polyphen
0.90
.;P;.;P;.;.;P;P;.;P;.;.;P
Vest4
0.74, 0.78, 0.71
MutPred
Loss of methylation at R84 (P = 0.0321);Loss of methylation at R84 (P = 0.0321);Loss of methylation at R84 (P = 0.0321);Loss of methylation at R84 (P = 0.0321);.;Loss of methylation at R84 (P = 0.0321);Loss of methylation at R84 (P = 0.0321);Loss of methylation at R84 (P = 0.0321);Loss of methylation at R84 (P = 0.0321);Loss of methylation at R84 (P = 0.0321);Loss of methylation at R84 (P = 0.0321);Loss of methylation at R84 (P = 0.0321);Loss of methylation at R84 (P = 0.0321);
MVP
MPC
1.0
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at