Genetic Variant ARSD:p.Gly505Arg (chrX-2907540-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001669.4(ARSD):c.1513G>A(p.Gly505Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,178,000 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00010 ( 0 hom. 39 hem. )

Consequence

ARSD
NM_001669.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97

Publications

0 publications found

Variant links:

Genes affected

ARSD (HGNC:717): (arylsulfatase D) The protein encoded by this gene is a member of the sulfatase family. Sulfatases are essential for the correct composition of bone and cartilage matrix. The encoded protein is postranslationally glycosylated and localized to the lysosome. This gene is located within a cluster of similar arylsulfatase genes on chromosome X. A related pseudogene has been identified in the pseudoautosomal region of chromosome Y. [provided by RefSeq, Jul 2011]

ARSD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.844

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001669.4. 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
	ARSD	NM_001669.4	MANE Select	c.1513G>A	p.Gly505Arg	missense	Exon 10 of 10	NP_001660.2	P51689-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARSD	ENST00000381154.6	TSL:1 MANE Select	c.1513G>A	p.Gly505Arg	missense	Exon 10 of 10	ENSP00000370546.1	P51689-1
ARSD	ENST00000954947.1		c.1378G>A	p.Gly460Arg	missense	Exon 9 of 9	ENSP00000625006.1
ARSD	ENST00000954948.1		c.1078G>A	p.Gly360Arg	missense	Exon 7 of 7	ENSP00000625007.1

Frequencies

GnomAD3 genomes

AF:

0.000115

AC:

AN:

112968

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000244

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000123

AC:

AN:

130600

AF XY:

0.000127

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:

0.0000817

Gnomad NFE exome

AF:

0.000253

Gnomad OTH exome

AF:

0.000298

GnomAD4 exome

AF:

0.0000995

AC:

106

AN:

1065032

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

338888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25801

American (AMR)

AF:

0.00

AC:

AN:

31134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17917

East Asian (EAS)

AF:

0.0000686

AC:

AN:

29144

South Asian (SAS)

AF:

0.0000204

AC:

AN:

49096

European-Finnish (FIN)

AF:

0.000154

AC:

AN:

38878

Middle Eastern (MID)

AF:

0.000502

AC:

AN:

3988

European-Non Finnish (NFE)

AF:

0.000110

AC:

AN:

824438

Other (OTH)

AF:

0.0000896

AC:

AN:

44636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.000115

AC:

AN:

112968

Hom.:

Cov.:

AF XY:

0.0000570

AC XY:

AN XY:

35102

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31168

American (AMR)

AF:

0.00

AC:

AN:

10776

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2663

East Asian (EAS)

AF:

0.00

AC:

AN:

3579

South Asian (SAS)

AF:

0.00

AC:

AN:

2757

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6281

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000244

AC:

AN:

53307

Other (OTH)

AF:

0.00

AC:

AN:

1513

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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:

0.000266

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.000142

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

Benign

-0.095

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.70

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.84

MetaSVM

Pathogenic

0.84

MutationAssessor

Uncertain

2.5

PhyloP100

3.0

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-7.5

REVEL

Uncertain

0.44

Sift

Uncertain

0.021

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.52

MutPred

0.61

Loss of glycosylation at S504 (P = 0.0455)

MVP

0.98

MPC

0.59

ClinPred

0.93

GERP RS

3.0

Varity_R

0.67

gMVP

0.79

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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