X-2915597-C-T

Position:

• chrX-2915597-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_001669.4(ARSD):​c.959G>A​(p.Gly320Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ARSD NM_001669.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.60

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021892011).
• BP6: Variant X-2915597-C-T is Benign according to our data. Variant chrX-2915597-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3060487.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSD	NM_001669.4	c.959G>A	p.Gly320Asp	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	c.959G>A	p.Gly320Asp	missense_variant	6/10	1	NM_001669.4	ENSP00000370546	P1
ARSD	ENST00000217890.10	n.959G>A		non_coding_transcript_exon_variant	6/7	1
ARSD	ENST00000481340.1	n.76-824G>A		intron_variant, non_coding_transcript_variant		3
ARSD	ENST00000495294.1	n.119-6792G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

Alfa AF: 0.212 Hom.: 0

ExAC AF: 0.196 AC: 23737

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ARSD-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 31, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	D
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.022	T
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	0.000042	P
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.28
MPC		0.72
ClinPred		0.90	D
GERP RS		3.7
Varity_R		0.89
gMVP		0.95

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

Other links and lift over

dbSNP: rs370769167; hg19: chrX-2833638; COSMIC: COSV54198357; COSMIC: COSV54198357;