Variant X-2907471-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARSD	NM_001669.4 linkuse as main transcript	c.1582C>T	p.Pro528Ser	missense_variant	10/10	ENST00000381154.6	NP_001660.2
ARSD	XM_005274514.3 linkuse as main transcript	c.1447C>T	p.Pro483Ser	missense_variant	9/9		XP_005274571.1
ARSD	XM_047442108.1 linkuse as main transcript	c.1444C>T	p.Pro482Ser	missense_variant	10/10		XP_047298064.1
ARSD	XM_005274515.3 linkuse as main transcript	c.*506C>T		3_prime_UTR_variant	10/10		XP_005274572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSD	ENST00000381154.6 linkuse as main transcript	c.1582C>T	p.Pro528Ser	missense_variant	10/10	1	NM_001669.4	ENSP00000370546	P1	P51689-1
ARSD	ENST00000458014.1 linkuse as main transcript	c.388C>T	p.Pro130Ser	missense_variant	3/4	3		ENSP00000409180
ARSD	ENST00000495294.1 linkuse as main transcript	n.717C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000887

AC:

AN:

112760

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34912

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

GnomAD3 exomes

AF:

0.0000117

AC:

AN:

171420

Hom.:

AF XY:

0.0000343

AC XY:

AN XY:

58254

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000574

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000476

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000886

AC:

AN:

112809

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34971

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000933

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2023

The c.1582C>T (p.P528S) alteration is located in exon 10 (coding exon 10) of the ARSD gene. This alteration results from a C to T substitution at nucleotide position 1582, causing the proline (P) at amino acid position 528 to be replaced by a serine (S). 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

0.16

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.70

D;.

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.77

T;T

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Uncertain

0.70

MutationAssessor

Uncertain

2.9

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.063

T;D

Polyphen

0.27

B;.

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

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

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