Variant rs200569213 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.844

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSD	NM_001669.4 link	c.1513G>A	p.Gly505Arg	missense_variant	Exon 10 of 10	ENST00000381154.6	NP_001660.2	P51689-1A0A140VK06
ARSD	XM_005274514.3 link	c.1378G>A	p.Gly460Arg	missense_variant	Exon 9 of 9		XP_005274571.1
ARSD	XM_047442108.1 link	c.1375G>A	p.Gly459Arg	missense_variant	Exon 10 of 10		XP_047298064.1
ARSD	XM_005274515.3 link	c.*437G>A		3_prime_UTR_variant	Exon 10 of 10		XP_005274572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARSD	ENST00000381154.6 link	c.1513G>A	p.Gly505Arg	missense_variant	Exon 10 of 10	1	NM_001669.4	ENSP00000370546.1	P51689-1
ARSD	ENST00000458014.1 link	c.319G>A	p.Gly107Arg	missense_variant	Exon 3 of 4	3		ENSP00000409180.1	H7C327
ARSD	ENST00000495294.1 link	n.648G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.000115

AC:

AN:

112968

Hom.:

Cov.:

AF XY:

0.0000570

AC XY:

AN XY:

35102

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

GnomAD3 exomes

AF:

0.000123

AC:

AN:

130600

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

31610

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000686

Gnomad4 SAS exome

AF:

0.0000204

Gnomad4 FIN exome

AF:

0.000154

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.0000896

GnomAD4 genome

AF:

0.000115

AC:

AN:

112968

Hom.:

Cov.:

AF XY:

0.0000570

AC XY:

AN XY:

35102

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000244

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000266

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.000142

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1513G>A (p.G505R) alteration is located in exon 10 (coding exon 10) of the ARSD gene. This alteration results from a G to A substitution at nucleotide position 1513, causing the glycine (G) at amino acid position 505 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.70

D;.

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.82

T;T

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Pathogenic

0.84

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-7.5

D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.022

D;D

Polyphen

1.0

D;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over