17-68271075-T-A

Variant names:

• chr17-68271075-T-A
• NM_004694.5:c.1085A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004694.5(SLC16A6):​c.1085A>T​(p.Glu362Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC16A6 NM_004694.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.59

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]

ACMG classification

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 rank	MANE	Protein	UniProt
SLC16A6	NM_004694.5	c.1085A>T	p.Glu362Val	missense_variant	Exon 5 of 6	ENST00000580666.6	NP_004685.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A6	ENST00000580666.6	c.1085A>T	p.Glu362Val	missense_variant	Exon 5 of 6	1	NM_004694.5	ENSP00000462985.1
SLC16A6	ENST00000327268.8	c.1085A>T	p.Glu362Val	missense_variant	Exon 6 of 7	1		ENSP00000319991.4
ARSG	ENST00000448504.6	c.-552+11649T>A		intron_variant	Intron 1 of 11	1		ENSP00000407193.2
ARSG	ENST00000578726.1	n.27-2815T>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727242

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: 0.0000464

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

Submissions by phenotype

not specified Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1085A>T (p.E362V) alteration is located in exon 6 (coding exon 4) of the SLC16A6 gene. This alteration results from a A to T substitution at nucleotide position 1085, causing the glutamic acid (E) at amino acid position 362 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	0.31
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T;T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.83	.;T;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.080	N;.;.
REVEL	Benign	0.19
Sift	Benign	0.54	T;.;.
Sift4G	Benign	0.44	T;T;T
Polyphen		0.65	P;P;.
Vest4		0.59
MutPred		0.69		Loss of ubiquitination at K358 (P = 0.0634);Loss of ubiquitination at K358 (P = 0.0634);Loss of ubiquitination at K358 (P = 0.0634);
MVP		0.78
MPC		1.3
ClinPred		0.62	D
GERP RS		4.4
Varity_R		0.16
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-66267216;