chr17-68269191-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004694.5(SLC16A6):c.1477C>T(p.Arg493Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,420,450 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000069 ( 0 hom., cov: 27)
Exomes 𝑓: 0.00011 ( 4 hom. )
Failed GnomAD Quality Control
Consequence
SLC16A6
NM_004694.5 missense
NM_004694.5 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: -0.0100
Genes affected
SLC16A6 (HGNC:10927): (solute carrier family 16 member 6) Predicted to enable monocarboxylic acid transmembrane transporter activity. Predicted to be involved in monocarboxylic acid transport. Predicted to be located in membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
ARSG (HGNC:24102): (arylsulfatase G) The protein encoded by this gene belongs to the sulfatase enzyme family. Sulfatases hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules. This protein displays arylsulfatase activity at acidic pH, as is typical of lysosomal sulfatases, and has been shown to localize in the lysosomes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.043620825).
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC16A6 | NM_004694.5 | c.1477C>T | p.Arg493Cys | missense_variant | 6/6 | ENST00000580666.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC16A6 | ENST00000580666.6 | c.1477C>T | p.Arg493Cys | missense_variant | 6/6 | 1 | NM_004694.5 | P1 | |
SLC16A6 | ENST00000327268.8 | c.1477C>T | p.Arg493Cys | missense_variant | 7/7 | 1 | P1 | ||
ARSG | ENST00000448504.6 | c.-552+9765G>A | intron_variant | 1 | P1 | ||||
ARSG | ENST00000578726.1 | n.27-4699G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000687 AC: 10AN: 145544Hom.: 0 Cov.: 27
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GnomAD3 exomes AF: 0.000147 AC: 32AN: 217600Hom.: 2 AF XY: 0.000220 AC XY: 26AN XY: 117948
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GnomAD4 exome AF: 0.000106 AC: 150AN: 1420450Hom.: 4 Cov.: 28 AF XY: 0.000166 AC XY: 117AN XY: 704530
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0000687 AC: 10AN: 145660Hom.: 0 Cov.: 27 AF XY: 0.0000990 AC XY: 7AN XY: 70734
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Data not reliable, filtered out with message: AS_VQSR
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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 | Jan 17, 2024 | The c.1477C>T (p.R493C) alteration is located in exon 7 (coding exon 5) of the SLC16A6 gene. This alteration results from a C to T substitution at nucleotide position 1477, causing the arginine (R) at amino acid position 493 to be replaced by a cysteine (C). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.
REVEL
Benign
Sift
Uncertain
D;.;.
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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