X-2934665-A-G

Position:

• chrX-2934665-A-G

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.*167T>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 0.00608 in 423,803 control chromosomes in the GnomAD database, including 47 homozygotes. There are 618 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (38 hom., 441 hem., cov: 22)
  • Exomes 𝑓: 0.0024 (9 hom. 177 hem.)
• Consequence: ARSL NM_000047.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.62

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=-0.89).
• BP6: Variant X-2934665-A-G is Benign according to our data. Variant chrX-2934665-A-G is described in ClinVar as [Benign]. Clinvar id is 1272237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSL	NM_000047.3	c.*167T>C		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.*167T>C		3_prime_UTR_variant	11/11	1	NM_000047.3	ENSP00000370526.3

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 1827 AN: 109787 Hom.: 38 Cov.: 22 AF XY: 0.0138 AC XY: 442 AN XY: 32117

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00791

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000391

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000304

Gnomad OTH AF: 0.0157

GnomAD4 exome AF: 0.00239 AC: 750 AN: 313968 Hom.: 9 Cov.: 4 AF XY: 0.00182 AC XY: 177 AN XY: 97330

Gnomad4 AFR exome AF: 0.0601

Gnomad4 AMR exome AF: 0.00383

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000439

Gnomad4 SAS exome AF: 0.000165

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000159

Gnomad4 OTH exome AF: 0.00520

GnomAD4 genome AF: 0.0166 AC: 1828 AN: 109835 Hom.: 38 Cov.: 22 AF XY: 0.0137 AC XY: 441 AN XY: 32175

Gnomad4 AFR AF: 0.0566

Gnomad4 AMR AF: 0.00790

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000392

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000304

Gnomad4 OTH AF: 0.0155

Alfa AF: 0.00275 Hom.: 7

Bravo AF: 0.0190

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	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5982927; hg19: chrX-2852706;