X-2960404-GTCTC-GTCTCTCTC

Variant names:

• chrX-2960404-G-GTCTC
• rs200332753
• NM_000047.3:c.-8_-5dupGAGA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001369079.1(ARSL):​c.20_23dupGAGA​(p.Asp8GlufsTer70) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 20)
• Consequence: ARSL NM_001369079.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

Genes affected

ARSL (HGNC:719): (arylsulfatase L) Arylsulfatase E is a member of the sulfatase family. It is glycosylated postranslationally and localized to the golgi apparatus. Sulfatases are essential for the correct composition of bone and cartilage matrix. X-linked chondrodysplasia punctata, a disease characterized by abnormalities in cartilage and bone development, has been linked to mutations in this gene. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on the Y chromosome. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.987 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSL	NM_000047.3	c.-8_-5dupGAGA		5_prime_UTR_variant	Exon 2 of 11	ENST00000381134.9	NP_000038.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSL	ENST00000381134.9	c.-8_-5dupGAGA		5_prime_UTR_variant	Exon 2 of 11	1	NM_000047.3	ENSP00000370526.3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200332753; hg19: chrX-2878445;