dbSNP rs760166650: ARSH:p.Arg109Cys (chrX-3013157-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001011719.2(ARSH):c.325C>T(p.Arg109Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,206,433 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.0000037 ( 0 hom. 1 hem. )

Consequence

ARSH
NM_001011719.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.233

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25823623).

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.325C>T	p.Arg109Cys	missense	Exon 3 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.325C>T	p.Arg109Cys	missense	Exon 3 of 9	ENSP00000370522.3	Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111397

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000284

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000168

AC:

AN:

178069

AF XY:

0.0000159

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000151

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000365

AC:

AN:

1095036

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

360536

show subpopulations

African (AFR)

AF:

0.0000381

AC:

AN:

26267

American (AMR)

AF:

0.00

AC:

AN:

34779

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19273

East Asian (EAS)

AF:

0.0000668

AC:

AN:

29929

South Asian (SAS)

AF:

0.00

AC:

AN:

53564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40455

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4117

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840696

Other (OTH)

AF:

0.0000218

AC:

AN:

45956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000180

AC:

AN:

111397

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33593

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30649

American (AMR)

AF:

0.00

AC:

AN:

10447

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.000284

AC:

AN:

3521

South Asian (SAS)

AF:

0.00

AC:

AN:

2619

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53104

Other (OTH)

AF:

0.00

AC:

AN:

1490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

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

0.18

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.54

FATHMM_MKL

Benign

0.035

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.26

MetaSVM

Uncertain

0.67

MutationAssessor

Benign

1.6

PhyloP100

0.23

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.46

Sift

Benign

0.034

Sift4G

Uncertain

0.033

Polyphen

0.010

Vest4

0.23

MutPred

0.62

Loss of MoRF binding (P = 0.016)

MVP

0.36

MPC

0.20

ClinPred

0.041

GERP RS

1.2

Varity_R

0.11

gMVP

0.87

Mutation Taster

=95/5

polymorphism

(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