Variant X-3015270-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000381130.3(ARSH):c.641G>A(p.Ser214Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00681 in 1,209,268 control chromosomes in the GnomAD database, including 330 homozygotes. There are 2,235 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 171 hom., 1056 hem., cov: 22)

Exomes 𝑓: 0.0039 ( 159 hom. 1179 hem. )

Consequence

ARSH
ENST00000381130.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.10

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023491979).

BP6

Variant X-3015270-G-A is Benign according to our data. Variant chrX-3015270-G-A is described in ClinVar as [Benign]. Clinvar id is 558983.Status of the report is criteria_provided_single_submitter, 1 stars.

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.641G>A	p.Ser214Asn	missense_variant	4/9	ENST00000381130.3	NP_001011719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSH	ENST00000381130.3 linkuse as main transcript	c.641G>A	p.Ser214Asn	missense_variant	4/9	1	NM_001011719.2	ENSP00000370522	P1

Frequencies

GnomAD3 genomes

AF:

0.0355

AC:

3947

AN:

111209

Hom.:

172

Cov.:

AF XY:

0.0315

AC XY:

1052

AN XY:

33435

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.0204

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000379

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.000414

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0103

AC:

1886

AN:

182722

Hom.:

AF XY:

0.00638

AC XY:

429

AN XY:

67200

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.00752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000212

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000589

Gnomad OTH exome

AF:

0.00509

GnomAD4 exome

AF:

0.00390

AC:

4279

AN:

1098006

Hom.:

159

Cov.:

AF XY:

0.00324

AC XY:

1179

AN XY:

363366

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.00898

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000259

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000272

Gnomad4 OTH exome

AF:

0.00933

GnomAD4 genome

AF:

0.0355

AC:

3952

AN:

111262

Hom.:

171

Cov.:

AF XY:

0.0315

AC XY:

1056

AN XY:

33498

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.0164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000381

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000414

Gnomad4 OTH

AF:

0.0297

Alfa

AF:

0.00409

Hom.:

162

Bravo

AF:

0.0411

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.128

AC:

491

ESP6500EA

AF:

0.000892

AC:

ExAC

AF:

0.0114

AC:

1382

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

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.55

FATHMM_MKL

Benign

0.086

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.88

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.38

Sift

Benign

0.31

Sift4G

Benign

0.31

Polyphen

0.97

Vest4

0.091

MPC

0.58

ClinPred

0.049

GERP RS

4.0

Varity_R

0.28

gMVP

0.86

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