Genetic Variant ARSH:p.Asn80Ser (chrX-3013071-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001011719.2(ARSH):c.239A>G(p.Asn80Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000951 in 1,208,680 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 62 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.00010 ( 0 hom. 62 hem. )

Consequence

ARSH
NM_001011719.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016371697).

BS2

High Hemizygotes in GnomAdExome4 at 62 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.239A>G	p.Asn80Ser	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.239A>G	p.Asn80Ser	missense	Exon 3 of 9	ENSP00000370522.3	Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.0000450

AC:

AN:

111187

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:

0.00

Gnomad SAS

AF:

0.00191

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000188

AC:

AN:

180904

AF XY:

0.000260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.000100

AC:

110

AN:

1097437

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

AN XY:

362831

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26352

American (AMR)

AF:

0.00

AC:

AN:

35115

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19349

East Asian (EAS)

AF:

0.00

AC:

AN:

30128

South Asian (SAS)

AF:

0.00191

AC:

103

AN:

54028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841743

Other (OTH)

AF:

0.000130

AC:

AN:

46071

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.0000449

AC:

AN:

111243

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33479

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30664

American (AMR)

AF:

0.00

AC:

AN:

10445

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2636

East Asian (EAS)

AF:

0.00

AC:

AN:

3510

South Asian (SAS)

AF:

0.00192

AC:

AN:

2610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6001

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52983

Other (OTH)

AF:

0.00

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

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:

0.0000508

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.000280

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

0.097

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.33

CADD

Benign

5.0

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.36

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.016

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

0.62

PhyloP100

1.8

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.29

Sift

Benign

0.40

Sift4G

Benign

0.40

Polyphen

0.013

Vest4

0.076

MutPred

0.58

Gain of MoRF binding (P = 0.1142)

MVP

0.56

MPC

0.12

ClinPred

0.017

GERP RS

2.2

Varity_R

0.096

gMVP

0.66

Mutation Taster

=98/2

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