rs12393627

Variant names:

• chrX-2967682-A-G
• rs12393627
• NM_001369080.1:c.-232+467T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369080.1. 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_001369080.1		c.-232+467T>C		intron	N/A	NP_001356009.1	F5GYY5
	ARSL	NM_001369079.1		c.7+467T>C		intron	N/A	NP_001356008.1
	ARSL	NM_001282631.2		c.-21+467T>C		intron	N/A	NP_001269560.2	A0A5F9ZHX8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSL	ENST00000672027.1		c.-232+467T>C		intron	N/A	ENSP00000500220.1	F5GYY5
	ARSL	ENST00000540563.6	TSL:2	c.-21+467T>C		intron	N/A	ENSP00000438198.2	P51690
	ARSL	ENST00000879212.1		c.-69+467T>C		intron	N/A	ENSP00000549271.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 11863 AN: 112386 Hom.: 1527 Cov.: 23

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

African (AFR) AF: 0.365 AC: 11233 AN: 30792

American (AMR) AF: 0.0380 AC: 405 AN: 10656

Ashkenazi Jewish (ASJ) AF: 0.00829 AC: 22 AN: 2655

East Asian (EAS) AF: 0.000558 AC: 2 AN: 3582

South Asian (SAS) AF: 0.00255 AC: 7 AN: 2747

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6222

Middle Eastern (MID) AF: 0.0323 AC: 7 AN: 217

European-Non Finnish (NFE) AF: 0.00150 AC: 80 AN: 53345

Other (OTH) AF: 0.0904 AC: 139 AN: 1538

Alfa AF: 0.0433 Hom.: 441

Bravo AF: 0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.33
PhyloP100		-1.3
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: rs12393627; hg19: chrX-2885723;