chr17-68271484-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004694.5(SLC16A6):ā€‹c.676C>Gā€‹(p.Leu226Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SLC16A6
NM_004694.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18402344).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC16A6NM_004694.5 linkuse as main transcriptc.676C>G p.Leu226Val missense_variant 5/6 ENST00000580666.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC16A6ENST00000580666.6 linkuse as main transcriptc.676C>G p.Leu226Val missense_variant 5/61 NM_004694.5 P1
SLC16A6ENST00000327268.8 linkuse as main transcriptc.676C>G p.Leu226Val missense_variant 6/71 P1
ARSGENST00000448504.6 linkuse as main transcriptc.-552+12058G>C intron_variant 1 P1
ARSGENST00000578726.1 linkuse as main transcriptn.27-2406G>C intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251466
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461854
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsNov 15, 2021The c.676C>G (p.L226V) alteration is located in exon 6 (coding exon 4) of the SLC16A6 gene. This alteration results from a C to G substitution at nucleotide position 676, causing the leucine (L) at amino acid position 226 to be replaced by a valine (V). 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
0.17
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.090
T;T;.
Eigen
Benign
-0.045
Eigen_PC
Benign
0.021
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.83
.;T;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
1.8
L;L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.83
N;.;.
REVEL
Benign
0.035
Sift
Benign
0.19
T;.;.
Sift4G
Benign
0.25
T;T;T
Polyphen
0.44
B;B;.
Vest4
0.11
MutPred
0.39
Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP
0.56
MPC
1.2
ClinPred
0.53
D
GERP RS
3.6
Varity_R
0.17
gMVP
0.45

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: rs1168203877; hg19: chr17-66267625; API