X-2934561-C-T

Position:

• chrX-2934561-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000047.3(ARSL):​c.*271G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 110,783 control chromosomes in the GnomAD database, including 248 homozygotes. There are 1,266 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (248 hom., 1266 hem., cov: 22)
  • Exomes 𝑓: 0.014 (91 hom. 813 hem.)
  • Failed GnomAD Quality Control
• Consequence: ARSL NM_000047.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.996

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]

ARSL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-2934561-C-T is Benign according to our data. Variant chrX-2934561-C-T is described in ClinVar as [Benign]. Clinvar id is 1262206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSL	NM_000047.3	c.*271G>A		3_prime_UTR_variant	11/11	ENST00000381134.9	NP_000038.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSL	ENST00000381134	c.*271G>A		3_prime_UTR_variant	11/11	1	NM_000047.3	ENSP00000370526.3

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 4916 AN: 110731 Hom.: 249 Cov.: 22 AF XY: 0.0381 AC XY: 1259 AN XY: 33017

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.00152

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.00795

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00424

Gnomad NFE AF: 0.00224

Gnomad OTH AF: 0.0424

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0141 AC: 3131 AN: 222773 Hom.: 91 AF XY: 0.0141 AC XY: 813 AN XY: 57795

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.0655

Gnomad4 ASJ exome AF: 0.00122

Gnomad4 EAS exome AF: 0.0453

Gnomad4 SAS exome AF: 0.00792

Gnomad4 FIN exome AF: 0.000195

Gnomad4 NFE exome AF: 0.00241

Gnomad4 OTH exome AF: 0.0206

GnomAD4 genome AF: 0.0444 AC: 4919 AN: 110783 Hom.: 248 Cov.: 22 AF XY: 0.0383 AC XY: 1266 AN XY: 33079

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0522

Gnomad4 ASJ AF: 0.00152

Gnomad4 EAS AF: 0.0263

Gnomad4 SAS AF: 0.00798

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00224

Gnomad4 OTH AF: 0.0418

Alfa AF: 0.0274 Hom.: 124

Bravo AF: 0.0552

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.8
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs139314733; hg19: chrX-2852602;