rs12393627

Positions:

• chrX-2967682-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369080.1(ARSL):​c.-232+467T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 112,438 control chromosomes in the GnomAD database, including 1,534 homozygotes. There are 3,338 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1534 hom., 3338 hem., cov: 23)
• Consequence: ARSL NM_001369080.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSL	NM_001282631.2	c.-21+467T>C		intron_variant			NP_001269560.2
ARSL	NM_001369079.1	c.7+467T>C		intron_variant			NP_001356008.1
ARSL	NM_001369080.1	c.-232+467T>C		intron_variant			NP_001356009.1
ARSL	XM_047442110.1	c.7+467T>C		intron_variant			XP_047298066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSL	ENST00000540563.6	c.-21+467T>C		intron_variant		2		ENSP00000438198	P4
ARSL	ENST00000672027.1	c.-232+467T>C		intron_variant				ENSP00000500220
ARSL	ENST00000672097.1	c.-21+467T>C		intron_variant				ENSP00000500727	A1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 11863 AN: 112386 Hom.: 1527 Cov.: 23 AF XY: 0.0957 AC XY: 3309 AN XY: 34566

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.0205

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.00829

Gnomad EAS AF: 0.000557

Gnomad SAS AF: 0.00327

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0336

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.0797

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 11909 AN: 112438 Hom.: 1534 Cov.: 23 AF XY: 0.0964 AC XY: 3338 AN XY: 34628

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.0380

Gnomad4 ASJ AF: 0.00829

Gnomad4 EAS AF: 0.000558

Gnomad4 SAS AF: 0.00255

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00150

Gnomad4 OTH AF: 0.0904

Alfa AF: 0.0433 Hom.: 441

Bravo AF: 0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12393627; hg19: chrX-2885723;