Variant X-3015016-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001011719.2(ARSH):c.387T>C(p.Cys129Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00684 in 1,209,716 control chromosomes in the GnomAD database, including 333 homozygotes. There are 2,260 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 173 hom., 1066 hem., cov: 22)

Exomes 𝑓: 0.0039 ( 160 hom. 1194 hem. )

Consequence

ARSH
NM_001011719.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.425

Variant links:

Genes affected

ARSH (HGNC:32488): (arylsulfatase family member H) Sulfatases, such as ARSH, hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005 [PubMed 16174644]).[supplied by OMIM, Mar 2008]

ARSH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant X-3015016-T-C is Benign according to our data. Variant chrX-3015016-T-C is described in ClinVar as [Benign]. Clinvar id is 558979.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.425 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSH	NM_001011719.2 linkuse as main transcript	c.387T>C	p.Cys129Cys	synonymous_variant	4/9	ENST00000381130.3	NP_001011719.1	Q5FYA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSH	ENST00000381130.3 linkuse as main transcript	c.387T>C	p.Cys129Cys	synonymous_variant	4/9	1	NM_001011719.2	ENSP00000370522.3		Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.0355

AC:

3961

AN:

111540

Hom.:

174

Cov.:

AF XY:

0.0315

AC XY:

1062

AN XY:

33740

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.0205

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00113

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.000433

Gnomad OTH

AF:

0.0284

GnomAD3 exomes

AF:

0.0104

AC:

1906

AN:

182980

Hom.:

AF XY:

0.00667

AC XY:

450

AN XY:

67462

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.00752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000588

Gnomad OTH exome

AF:

0.00530

GnomAD4 exome

AF:

0.00393

AC:

4314

AN:

1098123

Hom.:

160

Cov.:

AF XY:

0.00328

AC XY:

1194

AN XY:

363477

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.00898

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000277

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000273

Gnomad4 OTH exome

AF:

0.00968

GnomAD4 genome

AF:

0.0355

AC:

3966

AN:

111593

Hom.:

173

Cov.:

AF XY:

0.0315

AC XY:

1066

AN XY:

33803

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.0162

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00114

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000433

Gnomad4 OTH

AF:

0.0281

Alfa

AF:

0.0209

Hom.:

128

Bravo

AF:

0.0411

EpiCase

AF:

0.000818

EpiControl

AF:

0.000712

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Aug 30, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.2

DANN

Benign

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over