17-68269116-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004694.5(SLC16A6):c.1552G>A(p.Val518Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,515,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: SLC16A6 NM_004694.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.32

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04578927).
• BP6: Variant 17-68269116-C-T is Benign according to our data. Variant chr17-68269116-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2317226.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC16A6	NM_004694.5	c.1552G>A	p.Val518Met	missense_variant	6/6	ENST00000580666.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC16A6	ENST00000580666.6	c.1552G>A	p.Val518Met	missense_variant	6/6	1	NM_004694.5	P1
SLC16A6	ENST00000327268.8	c.1552G>A	p.Val518Met	missense_variant	7/7	1		P1
ARSG	ENST00000448504.6	c.-552+9690C>T		intron_variant		1		P1
ARSG	ENST00000578726.1	n.27-4774C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150706 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000454 AC: 8 AN: 176056 Hom.: 0 AF XY: 0.0000648 AC XY: 6 AN XY: 92614

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000966

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: 0.0000697

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000256 AC: 35 AN: 1364834 Hom.: 0 Cov.: 31 AF XY: 0.0000254 AC XY: 17 AN XY: 668754

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000699

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000253

Gnomad4 OTH exome AF: 0.0000178

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150824 Hom.: 0 Cov.: 28 AF XY: 0.0000136 AC XY: 1 AN XY: 73630

Gnomad4 AFR AF: 0.0000245

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.0000709 AC: 8

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	9.6
Dann	Benign	0.88
DEOGEN2	Benign	0.0057	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0093	N
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.18	N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.16	N;.;.
REVEL	Benign	0.020
Sift	Benign	0.33	T;.;.
Sift4G	Benign	0.30	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.029
MutPred		0.27		Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);.;
MVP		0.040
MPC		1.8
ClinPred		0.046	T
GERP RS		-6.0
Varity_R		0.030
gMVP		0.20

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

Other links and lift over

dbSNP: rs782052199; hg19: chr17-66265257; COSMIC: COSV100517162; COSMIC: COSV100517162;