X-3010084-C-T

Variant names:

• chrX-3010084-C-T
• rs79487908
• NM_001011719.2:c.147C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001011719.2(ARSH):​c.147C>T​(p.Leu49Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 1,209,085 control chromosomes in the GnomAD database, including 1,709 homozygotes. There are 23,970 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (116 hom., 1430 hem., cov: 22)
  • Exomes 𝑓: 0.062 (1593 hom. 22540 hem.)
• Consequence: ARSH NM_001011719.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.24
• Publications: 4 publications found

Genes affected

ARSH (HGNC:32488): (arylsulfatase family member H) Sulfatases, such as ARSH, hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005 [PubMed 16174644]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-3010084-C-T is Benign according to our data. Variant chrX-3010084-C-T is described in ClinVar as Benign. ClinVar VariationId is 558976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011719.2. 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
	ARSH	NM_001011719.2	MANE Select	c.147C>T	p.Leu49Leu	synonymous	Exon 2 of 9	NP_001011719.1	Q5FYA8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSH	ENST00000381130.3	TSL:1 MANE Select	c.147C>T	p.Leu49Leu	synonymous	Exon 2 of 9	ENSP00000370522.3	Q5FYA8

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 5037 AN: 111542 Hom.: 116 Cov.: 22

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.0337

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.00979

Gnomad SAS AF: 0.0270

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0546

Gnomad NFE AF: 0.0683

Gnomad OTH AF: 0.0439

GnomAD2 exomes AF: 0.0466 AC: 8538 AN: 183277 AF XY: 0.0486

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.0168

Gnomad ASJ exome AF: 0.0540

Gnomad EAS exome AF: 0.00649

Gnomad FIN exome AF: 0.0642

Gnomad NFE exome AF: 0.0670

Gnomad OTH exome AF: 0.0486

GnomAD4 exome AF: 0.0623 AC: 68413 AN: 1097487 Hom.: 1593 Cov.: 30 AF XY: 0.0621 AC XY: 22540 AN XY: 362945

African (AFR) AF: 0.0126 AC: 332 AN: 26382

American (AMR) AF: 0.0182 AC: 640 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 1113 AN: 19375

East Asian (EAS) AF: 0.00629 AC: 190 AN: 30204

South Asian (SAS) AF: 0.0361 AC: 1956 AN: 54109

European-Finnish (FIN) AF: 0.0676 AC: 2740 AN: 40516

Middle Eastern (MID) AF: 0.0401 AC: 166 AN: 4135

European-Non Finnish (NFE) AF: 0.0696 AC: 58607 AN: 841501

Other (OTH) AF: 0.0579 AC: 2669 AN: 46064

GnomAD4 genome AF: 0.0451 AC: 5034 AN: 111598 Hom.: 116 Cov.: 22 AF XY: 0.0423 AC XY: 1430 AN XY: 33774

African (AFR) AF: 0.0139 AC: 429 AN: 30802

American (AMR) AF: 0.0243 AC: 254 AN: 10470

Ashkenazi Jewish (ASJ) AF: 0.0541 AC: 143 AN: 2642

East Asian (EAS) AF: 0.0101 AC: 36 AN: 3564

South Asian (SAS) AF: 0.0267 AC: 70 AN: 2622

European-Finnish (FIN) AF: 0.0629 AC: 377 AN: 5995

Middle Eastern (MID) AF: 0.0507 AC: 11 AN: 217

European-Non Finnish (NFE) AF: 0.0683 AC: 3625 AN: 53079

Other (OTH) AF: 0.0433 AC: 66 AN: 1524

Alfa AF: 0.0438 Hom.: 842

Bravo AF: 0.0406

EpiCase AF: 0.0635

EpiControl AF: 0.0649

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.29
DANN	Benign	0.53
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs79487908; hg19: chrX-2928125; COSMIC: COSV66962960;