Variant X-2915565-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001669.4(ARSD):c.991T>G(p.Trp331Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,097,725 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000012 ( 0 hom. 5 hem. )

Consequence

ARSD
NM_001669.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSD	NM_001669.4 linkuse as main transcript	c.991T>G	p.Trp331Gly	missense_variant	6/10	ENST00000381154.6	NP_001660.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSD	ENST00000381154.6 linkuse as main transcript	c.991T>G	p.Trp331Gly	missense_variant	6/10	1	NM_001669.4	ENSP00000370546	P1	P51689-1
ARSD	ENST00000217890.10 linkuse as main transcript	n.991T>G		non_coding_transcript_exon_variant	6/7	1
ARSD	ENST00000481340.1 linkuse as main transcript	n.76-792T>G		intron_variant, non_coding_transcript_variant		3
ARSD	ENST00000495294.1 linkuse as main transcript	n.119-6760T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

183240

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67806

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:

0.000315

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1097725

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363219

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000203

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

Cov.:

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 04, 2023

The c.991T>G (p.W331G) alteration is located in exon 6 (coding exon 6) of the ARSD gene. This alteration results from a T to G substitution at nucleotide position 991, causing the tryptophan (W) at amino acid position 331 to be replaced by a glycine (G). 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

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Uncertain

0.73

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.61

MetaRNN

Uncertain

0.71

MetaSVM

Pathogenic

1.2

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.60

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-10

REVEL

Uncertain

0.57

Sift

Uncertain

0.017

Sift4G

Uncertain

0.054

Polyphen

0.21

Vest4

0.41

MutPred

0.57

Gain of disorder (P = 0.0101);

MVP

0.95

MPC

0.32

ClinPred

0.30

GERP RS

2.4

Varity_R

0.69

gMVP

0.89

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