rs5982927

Variant names:

• chrX-2934665-A-G
• rs5982927
• NM_000047.3:c.*167T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-2934665-A-G
• chrX-2934665-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• X-linked chondrodysplasia punctata 1

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000047.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSL	NM_000047.3	MANE Select	c.*167T>C		3_prime_UTR	Exon 11 of 11	NP_000038.2	P51690
	ARSL	NM_001282628.2		c.*167T>C		3_prime_UTR	Exon 12 of 12	NP_001269557.1	F5GYY5
	ARSL	NM_001369080.1		c.*167T>C		downstream_gene	N/A	NP_001356009.1	F5GYY5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSL	ENST00000381134.9	TSL:1 MANE Select	c.*167T>C		3_prime_UTR	Exon 11 of 11	ENSP00000370526.3	P51690
	ARSL	ENST00000681963.1		c.*167T>C		3_prime_UTR	Exon 12 of 12	ENSP00000507760.1	F5GYY5
	ARSL	ENST00000683290.1		c.*167T>C		3_prime_UTR	Exon 12 of 12	ENSP00000508156.1	F5GYY5

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 1827 AN: 109787 Hom.: 38 Cov.: 22

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

African (AFR) AF: 0.0601 AC: 571 AN: 9502

American (AMR) AF: 0.00383 AC: 47 AN: 12271

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9354

East Asian (EAS) AF: 0.0000439 AC: 1 AN: 22765

South Asian (SAS) AF: 0.000165 AC: 3 AN: 18132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32717

Middle Eastern (MID) AF: 0.000762 AC: 1 AN: 1312

European-Non Finnish (NFE) AF: 0.000159 AC: 30 AN: 189253

Other (OTH) AF: 0.00520 AC: 97 AN: 18662

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

African (AFR) AF: 0.0566 AC: 1707 AN: 30148

American (AMR) AF: 0.00790 AC: 81 AN: 10257

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2630

East Asian (EAS) AF: 0.00 AC: 0 AN: 3476

South Asian (SAS) AF: 0.000392 AC: 1 AN: 2549

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5713

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 211

European-Non Finnish (NFE) AF: 0.000304 AC: 16 AN: 52685

Other (OTH) AF: 0.0155 AC: 23 AN: 1488

Alfa AF: 0.00275 Hom.: 7

Bravo AF: 0.0190

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.48
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs5982927; hg19: chrX-2852706;