X-2934558-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000047.3(ARSL):c.*274G>C 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 111,025 control chromosomes in the GnomAD database, including 248 homozygotes. There are 1,277 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., 1277 hem., cov: 22)
  • Exomes 𝑓: 0.014 (92 hom. 809 hem.)
  • Failed GnomAD Quality Control
• Consequence: ARSL NM_000047.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0770

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-2934558-C-G is Benign according to our data. Variant chrX-2934558-C-G is described in ClinVar as [Benign]. Clinvar id is 1288825.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
ARSL	NM_000047.3	c.*274G>C		3_prime_UTR_variant	11/11	ENST00000381134.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSL	ENST00000381134.9	c.*274G>C		3_prime_UTR_variant	11/11	1	NM_000047.3	P4

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 4932 AN: 110974 Hom.: 249 Cov.: 22 AF XY: 0.0383 AC XY: 1271 AN XY: 33206

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.00152

Gnomad EAS AF: 0.0261

Gnomad SAS AF: 0.00791

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00422

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.0425

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0140 AC: 3114 AN: 222281 Hom.: 92 AF XY: 0.0140 AC XY: 809 AN XY: 57881

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0648

Gnomad4 ASJ exome AF: 0.00109

Gnomad4 EAS exome AF: 0.0449

Gnomad4 SAS exome AF: 0.00776

Gnomad4 FIN exome AF: 0.000197

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.0206

GnomAD4 genome AF: 0.0444 AC: 4934 AN: 111025 Hom.: 248 Cov.: 22 AF XY: 0.0384 AC XY: 1277 AN XY: 33267

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0520

Gnomad4 ASJ AF: 0.00152

Gnomad4 EAS AF: 0.0262

Gnomad4 SAS AF: 0.00793

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00226

Gnomad4 OTH AF: 0.0419

Alfa AF: 0.0274 Hom.: 124

Bravo AF: 0.0552

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	4.0
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs146382452; hg19: chrX-2852599;