Genetic Variant ARSH:p.Pro144Thr (chrX-3015059-C-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001011719.2(ARSH):c.430C>A(p.Pro144Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00713 in 1,208,826 control chromosomes in the GnomAD database, including 40 homozygotes. There are 2,791 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 6 hom., 209 hem., cov: 22)

Exomes 𝑓: 0.0073 ( 34 hom. 2582 hem. )

Consequence

ARSH
NM_001011719.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.54

Publications

7 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011798948).

BP6

Variant X-3015059-C-A is Benign according to our data. Variant chrX-3015059-C-A is described in ClinVar as Benign. ClinVar VariationId is 713928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 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.430C>A	p.Pro144Thr	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.430C>A	p.Pro144Thr	missense	Exon 4 of 9	ENSP00000370522.3	Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.00558

AC:

620

AN:

111107

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000851

Gnomad AMI

AF:

0.0869

Gnomad AMR

AF:

0.000964

Gnomad ASJ

AF:

0.00265

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.000771

Gnomad FIN

AF:

0.0276

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00655

Gnomad OTH

AF:

0.00200

GnomAD2 exomes

AF:

0.00649

AC:

1181

AN:

182092

AF XY:

0.00665

show subpopulations

Gnomad AFR exome

AF:

0.000916

Gnomad AMR exome

AF:

0.000476

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0287

Gnomad NFE exome

AF:

0.00774

Gnomad OTH exome

AF:

0.00731

GnomAD4 exome

AF:

0.00729

AC:

8003

AN:

1097666

Hom.:

Cov.:

AF XY:

0.00711

AC XY:

2582

AN XY:

363034

show subpopulations

African (AFR)

AF:

0.000644

AC:

AN:

26399

American (AMR)

AF:

0.000682

AC:

AN:

35173

Ashkenazi Jewish (ASJ)

AF:

0.00191

AC:

AN:

19380

East Asian (EAS)

AF:

0.00

AC:

AN:

30200

South Asian (SAS)

AF:

0.00157

AC:

AN:

53997

European-Finnish (FIN)

AF:

0.0262

AC:

1062

AN:

40503

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00774

AC:

6515

AN:

841799

Other (OTH)

AF:

0.00566

AC:

261

AN:

46085

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

332

664

995

1327

1659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

242

484

726

968

1210

<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:

0.00558

AC:

620

AN:

111160

Hom.:

Cov.:

AF XY:

0.00626

AC XY:

209

AN XY:

33370

show subpopulations

African (AFR)

AF:

0.000849

AC:

AN:

30638

American (AMR)

AF:

0.000963

AC:

AN:

10386

Ashkenazi Jewish (ASJ)

AF:

0.00265

AC:

AN:

2641

East Asian (EAS)

AF:

0.000283

AC:

AN:

3529

South Asian (SAS)

AF:

0.000774

AC:

AN:

2584

European-Finnish (FIN)

AF:

0.0276

AC:

165

AN:

5968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00655

AC:

347

AN:

53002

Other (OTH)

AF:

0.00198

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

117

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:

0.00528

Hom.:

264

Bravo

AF:

0.00381

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00658

AC:

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00684

AC:

ExAC

AF:

0.00649

AC:

788

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Pathogenic

0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.012

MetaSVM

Uncertain

0.72

MutationAssessor

Benign

1.8

PhyloP100

6.5

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-7.2

REVEL

Uncertain

0.62

Sift

Benign

0.072

Sift4G

Benign

0.068

Polyphen

0.83

Vest4

0.28

MVP

0.56

MPC

0.61

ClinPred

0.10

GERP RS

3.9

Varity_R

0.47

gMVP

0.92

Mutation Taster

=87/13

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