rs78142040

Variant names:

• chrX-2914730-C-T
• rs78142040
• ENST00000217890.10:n.1044G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000217890.10(ARSD):​n.1044G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 913,840 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 1 hem.)
• Consequence: ARSD ENST00000217890.10 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 6 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSD	NM_001669.4	c.1000+826G>A		intron_variant	Intron 6 of 9	ENST00000381154.6	NP_001660.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSD	ENST00000217890.10	n.1044G>A		non_coding_transcript_exon_variant	Exon 7 of 7	1
ARSD	ENST00000381154.6	c.1000+826G>A		intron_variant	Intron 6 of 9	1	NM_001669.4	ENSP00000370546.1
ARSD	ENST00000481340.1	n.119G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
ARSD	ENST00000495294.1	n.119-5925G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000834 AC: 1 AN: 119859 AF XY: 0.000233

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 5 AN: 913840 Hom.: 0 Cov.: 30 AF XY: 0.00000333 AC XY: 1 AN XY: 300708

African (AFR) AF: 0.00 AC: 0 AN: 20780

American (AMR) AF: 0.00 AC: 0 AN: 29545

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12682

East Asian (EAS) AF: 0.00 AC: 0 AN: 12773

South Asian (SAS) AF: 0.0000193 AC: 1 AN: 51855

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24585

Middle Eastern (MID) AF: 0.000311 AC: 1 AN: 3216

European-Non Finnish (NFE) AF: 0.00000414 AC: 3 AN: 724902

Other (OTH) AF: 0.00 AC: 0 AN: 33502

GnomAD4 genome Cov.: 23

Alfa AF: 0.128 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.060
DANN	Benign	0.34
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs78142040; hg19: chrX-2832771; COSMIC: COSV54200115; COSMIC: COSV54200115;