Genetic Variant ARSH:p.Arg125Trp (chrX-3015002-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001011719.2(ARSH):c.373C>T(p.Arg125Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000091 in 1,209,402 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000091 ( 0 hom. 4 hem. )

Consequence

ARSH
NM_001011719.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.351

Publications

3 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011719.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSH	NM_001011719.2	MANE Select	c.373C>T	p.Arg125Trp	missense	Exon 4 of 9	NP_001011719.1	Q5FYA8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSH	ENST00000381130.3	TSL:1 MANE Select	c.373C>T	p.Arg125Trp	missense	Exon 4 of 9	ENSP00000370522.3	Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111701

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000110

AC:

AN:

182193

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1097701

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363065

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26395

American (AMR)

AF:

0.0000284

AC:

AN:

35170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19363

East Asian (EAS)

AF:

0.00

AC:

AN:

30199

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54007

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4100

European-Non Finnish (NFE)

AF:

0.00000594

AC:

AN:

841870

Other (OTH)

AF:

0.00

AC:

AN:

46066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.00000895

AC:

AN:

111701

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33871

show subpopulations

African (AFR)

AF:

0.0000325

AC:

AN:

30767

American (AMR)

AF:

0.00

AC:

AN:

10435

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3571

South Asian (SAS)

AF:

0.00

AC:

AN:

2645

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53142

Other (OTH)

AF:

0.00

AC:

AN:

1509

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Uncertain

0.050

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

FATHMM_MKL

Benign

0.030

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.59

MetaRNN

Uncertain

0.67

MetaSVM

Pathogenic

0.85

MutationAssessor

Uncertain

2.1

PhyloP100

0.35

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.43

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.38

MutPred

0.66

Loss of loop (P = 0.0203)

MVP

0.26

MPC

0.64

ClinPred

0.90

GERP RS

0.38

Varity_R

0.33

gMVP

0.85

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

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

Publications

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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