rs782052199

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004694.5(SLC16A6):c.1552G>C(p.Val518Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000044 in 1,364,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V518M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

SLC16A6
NM_004694.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.32

Publications

1 publications found

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]

SLC16A6 links:

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]

ARSG Gene-Disease associations (from GenCC):

Usher syndrome, type 4
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
Usher syndrome type 3
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ARSG links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056895167).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004694.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC16A6	NM_004694.5	MANE Select	c.1552G>C	p.Val518Leu	missense	Exon 6 of 6	NP_004685.2
SLC16A6	NM_001174166.2		c.1552G>C	p.Val518Leu	missense	Exon 7 of 7	NP_001167637.1	O15403
ARSG	NM_014960.5		c.-552+9690C>G		intron	N/A	NP_055775.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC16A6	ENST00000580666.6	TSL:1 MANE Select	c.1552G>C	p.Val518Leu	missense	Exon 6 of 6	ENSP00000462985.1	O15403
SLC16A6	ENST00000327268.8	TSL:1	c.1552G>C	p.Val518Leu	missense	Exon 7 of 7	ENSP00000319991.4	O15403
ARSG	ENST00000448504.6	TSL:1	c.-552+9690C>G		intron	N/A	ENSP00000407193.2	Q96EG1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000440

AC:

AN:

1364840

Hom.:

Cov.:

AF XY:

0.00000299

AC XY:

AN XY:

668758

show subpopulations

African (AFR)

AF:

0.0000999

AC:

AN:

30024

American (AMR)

AF:

0.00

AC:

AN:

28636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19854

East Asian (EAS)

AF:

0.00

AC:

AN:

38686

South Asian (SAS)

AF:

0.00

AC:

AN:

69506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5292

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1066904

Other (OTH)

AF:

0.0000178

AC:

AN:

56092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.6

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.012

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.52

M_CAP

Benign

0.0045

MetaRNN

Benign

0.057

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

PhyloP100

-1.3

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.39

REVEL

Benign

0.013

Sift

Benign

0.27

Sift4G

Benign

0.78

Polyphen

0.0020

Vest4

0.031

MutPred

0.24

Loss of sheet (P = 0.0315)

MVP

0.040

MPC

1.8

ClinPred

0.11

GERP RS

-6.0

Varity_R

0.043

gMVP

0.19

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over