Variant X-3015025-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001011719.2(ARSH):c.396G>C(p.Pro132Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,209,357 control chromosomes in the GnomAD database, including 4 homozygotes. There are 1,022 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., 51 hem., cov: 22)

Exomes 𝑓: 0.0021 ( 4 hom. 971 hem. )

Consequence

ARSH
NM_001011719.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.57

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-3015025-G-C is Benign according to our data. Variant chrX-3015025-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 558980.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.57 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 51 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSH	NM_001011719.2 linkuse as main transcript	c.396G>C	p.Pro132Pro	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.396G>C	p.Pro132Pro	synonymous_variant	4/9	1	NM_001011719.2	ENSP00000370522.3		Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.00134

AC:

149

AN:

111274

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

AN XY:

33488

show subpopulations

Gnomad AFR

AF:

0.000228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000771

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0115

Gnomad FIN

AF:

0.000167

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00192

Gnomad OTH

AF:

0.000668

GnomAD3 exomes

AF:

0.00250

AC:

458

AN:

182930

Hom.:

AF XY:

0.00347

AC XY:

234

AN XY:

67412

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.0147

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.00162

Gnomad OTH exome

AF:

0.00243

GnomAD4 exome

AF:

0.00215

AC:

2356

AN:

1098028

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

971

AN XY:

363388

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.000795

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0138

Gnomad4 FIN exome

AF:

0.000123

Gnomad4 NFE exome

AF:

0.00173

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00135

AC:

150

AN:

111329

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

AN XY:

33553

show subpopulations

Gnomad4 AFR

AF:

0.000228

Gnomad4 AMR

AF:

0.000770

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0119

Gnomad4 FIN

AF:

0.000167

Gnomad4 NFE

AF:

0.00192

Gnomad4 OTH

AF:

0.000660

Alfa

AF:

0.000620

Hom.:

Bravo

AF:

0.000982

EpiCase

AF:

0.00256

EpiControl

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Sep 27, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.5

DANN

Benign

0.47

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