NM_001011719.2:c.396G>A

Variant names:

• chrX-3015025-G-A
• rs61746890
• NM_001011719.2:c.396G>A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001011719.2(ARSH):​c.396G>A​(p.Pro132Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 1,209,358 control chromosomes in the GnomAD database, including 4 homozygotes. There are 1,192 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 0.0017 (0 hom., 47 hem., cov: 22)
  • Exomes 𝑓: 0.0035 (4 hom. 1145 hem.)
• Consequence: ARSH NM_001011719.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57

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

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-2.57 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 47 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSH	NM_001011719.2	c.396G>A	p.Pro132Pro	synonymous_variant	Exon 4 of 9	ENST00000381130.3	NP_001011719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSH	ENST00000381130.3	c.396G>A	p.Pro132Pro	synonymous_variant	Exon 4 of 9	1	NM_001011719.2	ENSP00000370522.3

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 187 AN: 111274 Hom.: 0 Cov.: 22 AF XY: 0.00140 AC XY: 47 AN XY: 33488

Gnomad AFR AF: 0.000490

Gnomad AMI AF: 0.00442

Gnomad AMR AF: 0.000289

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000167

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00309

Gnomad OTH AF: 0.000668

GnomAD3 exomes AF: 0.00175 AC: 321 AN: 182930 Hom.: 0 AF XY: 0.00166 AC XY: 112 AN XY: 67412

Gnomad AFR exome AF: 0.000836

Gnomad AMR exome AF: 0.000182

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000125

Gnomad NFE exome AF: 0.00365

Gnomad OTH exome AF: 0.00110

GnomAD4 exome AF: 0.00346 AC: 3794 AN: 1098029 Hom.: 4 Cov.: 31 AF XY: 0.00315 AC XY: 1145 AN XY: 363387

Gnomad4 AFR exome AF: 0.000720

Gnomad4 AMR exome AF: 0.000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000247

Gnomad4 NFE exome AF: 0.00433

Gnomad4 OTH exome AF: 0.00250

GnomAD4 genome AF: 0.00168 AC: 187 AN: 111329 Hom.: 0 Cov.: 22 AF XY: 0.00140 AC XY: 47 AN XY: 33553

Gnomad4 AFR AF: 0.000489

Gnomad4 AMR AF: 0.000289

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000167

Gnomad4 NFE AF: 0.00309

Gnomad4 OTH AF: 0.000660

Alfa AF: 0.000765 Hom.: 7

Bravo AF: 0.00168

EpiCase AF: 0.00354

EpiControl AF: 0.00303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs61746890; hg19: chrX-2933066;