X-3010129-C-T

Variant names:

• chrX-3010129-C-T
• rs77183343
• NM_001011719.2:c.192C>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.192C>T​(p.Thr64Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,208,646 control chromosomes in the GnomAD database, including 5,004 homozygotes. There are 41,787 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.099 (432 hom., 3110 hem., cov: 22)
  • Exomes 𝑓: 0.11 (4572 hom. 38677 hem.)
• Consequence: ARSH NM_001011719.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -4.07
• Publications: 2 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=-0.93).
• BP6: Variant X-3010129-C-T is Benign according to our data. Variant chrX-3010129-C-T is described in ClinVar as Benign. ClinVar VariationId is 558977.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 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.192C>T	p.Thr64Thr	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.192C>T	p.Thr64Thr	synonymous	Exon 2 of 9	ENSP00000370522.3	Q5FYA8

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 11020 AN: 111380 Hom.: 432 Cov.: 22

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0736

Gnomad EAS AF: 0.00922

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.0866

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0957

GnomAD2 exomes AF: 0.0851 AC: 15484 AN: 182056 AF XY: 0.0859

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.0314

Gnomad ASJ exome AF: 0.0719

Gnomad EAS exome AF: 0.00651

Gnomad FIN exome AF: 0.0904

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.0808

GnomAD4 exome AF: 0.107 AC: 117670 AN: 1097213 Hom.: 4572 Cov.: 31 AF XY: 0.107 AC XY: 38677 AN XY: 362701

African (AFR) AF: 0.106 AC: 2787 AN: 26393

American (AMR) AF: 0.0355 AC: 1247 AN: 35139

Ashkenazi Jewish (ASJ) AF: 0.0762 AC: 1475 AN: 19368

East Asian (EAS) AF: 0.00480 AC: 145 AN: 30195

South Asian (SAS) AF: 0.0745 AC: 4028 AN: 54036

European-Finnish (FIN) AF: 0.0953 AC: 3857 AN: 40493

Middle Eastern (MID) AF: 0.0898 AC: 371 AN: 4132

European-Non Finnish (NFE) AF: 0.118 AC: 99019 AN: 841398

Other (OTH) AF: 0.103 AC: 4741 AN: 46059

GnomAD4 genome AF: 0.0989 AC: 11019 AN: 111433 Hom.: 432 Cov.: 22 AF XY: 0.0924 AC XY: 3110 AN XY: 33659

African (AFR) AF: 0.101 AC: 3087 AN: 30673

American (AMR) AF: 0.0516 AC: 540 AN: 10459

Ashkenazi Jewish (ASJ) AF: 0.0736 AC: 195 AN: 2648

East Asian (EAS) AF: 0.00953 AC: 34 AN: 3567

South Asian (SAS) AF: 0.0641 AC: 168 AN: 2622

European-Finnish (FIN) AF: 0.0866 AC: 517 AN: 5968

Middle Eastern (MID) AF: 0.133 AC: 29 AN: 218

European-Non Finnish (NFE) AF: 0.118 AC: 6268 AN: 53076

Other (OTH) AF: 0.0939 AC: 143 AN: 1523

Alfa AF: 0.111 Hom.: 1191

Bravo AF: 0.0969

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	-0.93
CADD	Benign	0.30
DANN	Benign	0.61
PhyloP100		-4.1
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: rs77183343; hg19: chrX-2928170; COSMIC: COSV66962965;