Variant X-3015192-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001011719.2(ARSH):c.563G>A(p.Arg188His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,207,986 control chromosomes in the GnomAD database, including 121 homozygotes. There are 5,889 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.010 ( 5 hom., 299 hem., cov: 22)

Exomes 𝑓: 0.015 ( 116 hom. 5590 hem. )

Consequence

ARSH
NM_001011719.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.302

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=0.0049436092).

BP6

Variant X-3015192-G-A is Benign according to our data. Variant chrX-3015192-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 558982.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-3015192-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0102 (1141/111440) while in subpopulation NFE AF= 0.0173 (916/53087). AF 95% confidence interval is 0.0163. There are 5 homozygotes in gnomad4. There are 299 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSH	NM_001011719.2 link	c.563G>A	p.Arg188His	missense_variant	Exon 4 of 9	ENST00000381130.3	NP_001011719.1	Q5FYA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSH	ENST00000381130.3 link	c.563G>A	p.Arg188His	missense_variant	Exon 4 of 9	1	NM_001011719.2	ENSP00000370522.3		Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1141

AN:

111389

Hom.:

Cov.:

AF XY:

0.00891

AC XY:

299

AN XY:

33557

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00583

Gnomad AMR

AF:

0.00442

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.00909

Gnomad FIN

AF:

0.00549

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0107

GnomAD3 exomes

AF:

0.0115

AC:

2051

AN:

177648

Hom.:

AF XY:

0.0127

AC XY:

797

AN XY:

62554

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00446

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0102

Gnomad FIN exome

AF:

0.00840

Gnomad NFE exome

AF:

0.0184

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0154

AC:

16854

AN:

1096546

Hom.:

116

Cov.:

AF XY:

0.0154

AC XY:

5590

AN XY:

362078

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00525

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0106

Gnomad4 FIN exome

AF:

0.00719

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0140

GnomAD4 genome

AF:

0.0102

AC:

1141

AN:

111440

Hom.:

Cov.:

AF XY:

0.00889

AC XY:

299

AN XY:

33618

show subpopulations

Gnomad4 AFR

AF:

0.00196

Gnomad4 AMR

AF:

0.00441

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00912

Gnomad4 FIN

AF:

0.00549

Gnomad4 NFE

AF:

0.0173

Gnomad4 OTH

AF:

0.0105

Alfa

AF:

0.0169

Hom.:

736

Bravo

AF:

0.00983

TwinsUK

AF:

0.0151

AC:

ALSPAC

AF:

0.0156

AC:

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.0175

AC:

118

ExAC

AF:

0.0125

AC:

1522

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.2

DANN

Benign

0.67

DEOGEN2

Benign

0.39

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.64

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.63

REVEL

Benign

0.22

Sift

Benign

0.24

Sift4G

Benign

0.16

Polyphen

0.0070

Vest4

0.023

MPC

0.18

ClinPred

0.0014

GERP RS

3.0

Varity_R

0.033

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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