Variant X-2910769-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001669.4(ARSD):c.1025A>C(p.Asp342Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000356 in 112,381 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)

Consequence

ARSD
NM_001669.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.487

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11256009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSD	NM_001669.4 link	c.1025A>C	p.Asp342Ala	missense_variant	Exon 7 of 10	ENST00000381154.6	NP_001660.2	P51689-1A0A140VK06
ARSD	XM_047442108.1 link	c.887A>C	p.Asp296Ala	missense_variant	Exon 7 of 10		XP_047298064.1
ARSD	XM_005274515.3 link	c.1025A>C	p.Asp342Ala	missense_variant	Exon 7 of 10		XP_005274572.1
ARSD	XM_005274514.3 link	c.1001-790A>C		intron_variant	Intron 6 of 8		XP_005274571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSD	ENST00000381154.6 link	c.1025A>C	p.Asp342Ala	missense_variant	Exon 7 of 10	1	NM_001669.4	ENSP00000370546.1		P51689-1
ARSD	ENST00000495294.1 link	n.119-1964A>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0000356

AC:

AN:

112381

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34523

show subpopulations

Gnomad AFR

AF:

0.000129

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

181973

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66457

show subpopulations

Gnomad AFR exome

AF:

0.000153

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000356

AC:

AN:

112381

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34523

show subpopulations

Gnomad4 AFR

AF:

0.000129

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000340

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

Jun 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1025A>C (p.D342A) alteration is located in exon 7 (coding exon 7) of the ARSD gene. This alteration results from a A to C substitution at nucleotide position 1025, causing the aspartic acid (D) at amino acid position 342 to be replaced by an alanine (A). 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

0.067

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.27

CADD

Benign

5.0

DANN

Benign

0.57

DEOGEN2

Uncertain

0.53

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.20

M_CAP

Benign

0.020

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.34

MutationAssessor

Benign

0.59

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Benign

0.20

Sift4G

Benign

0.28

Polyphen

0.022

Vest4

0.23

MVP

0.98

MPC

0.20

ClinPred

0.022

GERP RS

3.4

Varity_R

0.11

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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