Genetic Variant ARSD:c.1000+882A>G (chrX-2914674-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_009589.5(ARSD):c.1100A>G(p.Lys367Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000037 in 1,026,096 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000034 ( 0 hom. 9 hem. )

Consequence

ARSD
NM_009589.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.530

Publications

7 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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.027).

BP6

Variant X-2914674-T-C is Benign according to our data. Variant chrX-2914674-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3059497.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_009589.5. 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.1000+882A>G		intron	N/A	NP_001660.2	P51689-1
	ARSD	NM_009589.5		c.1100A>G	p.Lys367Arg	missense	Exon 7 of 7	NP_033667.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARSD	ENST00000381154.6	TSL:1 MANE Select	c.1000+882A>G	intron	N/A	ENSP00000370546.1	P51689-1
ARSD	ENST00000217890.10	TSL:1	n.1100A>G	non_coding_transcript_exon	Exon 7 of 7
ARSD	ENST00000954947.1		c.1000+882A>G	intron	N/A	ENSP00000625006.1

Frequencies

GnomAD3 genomes

AF:

0.0000625

AC:

AN:

111985

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:

0.000988

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000148

AC:

AN:

121945

AF XY:

0.000470

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:

0.00124

Gnomad NFE exome

AF:

0.0000564

Gnomad OTH exome

AF:

0.000318

GnomAD4 exome

AF:

0.0000339

AC:

AN:

914111

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

300975

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20789

American (AMR)

AF:

0.00

AC:

AN:

29552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12693

East Asian (EAS)

AF:

0.00

AC:

AN:

12774

South Asian (SAS)

AF:

0.00

AC:

AN:

51906

European-Finnish (FIN)

AF:

0.000976

AC:

AN:

24585

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3218

European-Non Finnish (NFE)

AF:

0.00000414

AC:

AN:

725085

Other (OTH)

AF:

0.000119

AC:

AN:

33509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

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:

0.0000625

AC:

AN:

111985

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34151

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30787

American (AMR)

AF:

0.00

AC:

AN:

10486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3594

South Asian (SAS)

AF:

0.00

AC:

AN:

2698

European-Finnish (FIN)

AF:

0.000988

AC:

AN:

6074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53258

Other (OTH)

AF:

0.00

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.120

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ARSD-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.20

(source)

DANN

Benign

0.29

PhyloP100

-0.53

Mutation Taster

=100/0

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

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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