Genetic Variant ARSH:p.Pro132Pro (chrX-3015025-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_001011719.2(ARSH):c.396G>A(p.Pro132Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 1,209,358 control chromosomes in the GnomAD database, including 4 homozygotes. There are 1,192 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P132P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., 47 hem., cov: 22)

Exomes 𝑓: 0.0035 ( 4 hom. 1145 hem. )

Consequence

ARSH
NM_001011719.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.57

Publications

2 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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

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

BS2

High Hemizygotes in GnomAd4 at 47 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.396G>A	p.Pro132Pro	synonymous	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.396G>A	p.Pro132Pro	synonymous	Exon 4 of 9	ENSP00000370522.3	Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

187

AN:

111274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000490

Gnomad AMI

AF:

0.00442

Gnomad AMR

AF:

0.000289

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000167

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.000668

GnomAD2 exomes

AF:

0.00175

AC:

321

AN:

182930

AF XY:

0.00166

show subpopulations

Gnomad AFR exome

AF:

0.000836

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.00365

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.00346

AC:

3794

AN:

1098029

Hom.:

Cov.:

AF XY:

0.00315

AC XY:

1145

AN XY:

363387

show subpopulations

African (AFR)

AF:

0.000720

AC:

AN:

26402

American (AMR)

AF:

0.000227

AC:

AN:

35202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54078

European-Finnish (FIN)

AF:

0.000247

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.00433

AC:

3642

AN:

842025

Other (OTH)

AF:

0.00250

AC:

115

AN:

46085

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

163

326

490

653

816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<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:

0.00168

AC:

187

AN:

111329

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

AN XY:

33553

show subpopulations

African (AFR)

AF:

0.000489

AC:

AN:

30706

American (AMR)

AF:

0.000289

AC:

AN:

10391

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2601

European-Finnish (FIN)

AF:

0.000167

AC:

AN:

5999

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00309

AC:

164

AN:

53034

Other (OTH)

AF:

0.000660

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000765

Hom.:

Bravo

AF:

0.00168

EpiCase

AF:

0.00354

EpiControl

AF:

0.00303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.7

(source)

DANN

Benign

0.63

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over