Genetic Variant ARSD:p.Pro528Ser (chrX-2907471-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001669.4(ARSD):c.1582C>T(p.Pro528Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000058 in 1,207,667 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.0000055 ( 0 hom. 1 hem. )

Consequence

ARSD
NM_001669.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.56

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.1582C>T	p.Pro528Ser	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.1582C>T	p.Pro528Ser	missense	Exon 10 of 10	ENSP00000370546.1	P51689-1
ARSD	ENST00000954947.1		c.1447C>T	p.Pro483Ser	missense	Exon 9 of 9	ENSP00000625006.1
ARSD	ENST00000954948.1		c.1147C>T	p.Pro383Ser	missense	Exon 7 of 7	ENSP00000625007.1

Frequencies

GnomAD3 genomes

AF:

0.00000887

AC:

AN:

112760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000934

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000117

AC:

AN:

171420

AF XY:

0.0000343

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1094858

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

360486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26355

American (AMR)

AF:

0.0000574

AC:

AN:

34844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19271

East Asian (EAS)

AF:

0.00

AC:

AN:

30103

South Asian (SAS)

AF:

0.00

AC:

AN:

53439

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40217

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4127

European-Non Finnish (NFE)

AF:

0.00000476

AC:

AN:

840543

Other (OTH)

AF:

0.00

AC:

AN:

45959

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

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:

0.00000886

AC:

AN:

112809

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34971

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31174

American (AMR)

AF:

0.0000933

AC:

AN:

10722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2657

East Asian (EAS)

AF:

0.00

AC:

AN:

3557

South Asian (SAS)

AF:

0.00

AC:

AN:

2715

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53290

Other (OTH)

AF:

0.00

AC:

AN:

1533

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

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

0.16

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.70

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.51

MetaSVM

Uncertain

0.70

MutationAssessor

Uncertain

2.9

PhyloP100

6.6

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.45

Sift

Uncertain

0.0080

Sift4G

Benign

0.063

Polyphen

0.27

Vest4

0.25

MutPred

0.50

Gain of phosphorylation at P528 (P = 0.0172)

MVP

0.93

MPC

0.25

ClinPred

0.76

GERP RS

3.0

Varity_R

0.39

gMVP

0.77

Mutation Taster

=81/19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over