Variant X-3006595-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001011719.2(ARSH):c.-18G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 1,193,877 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 223 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.00067 ( 0 hom. 218 hem. )

Consequence

ARSH
NM_001011719.2 5_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.768

Variant links:

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]

ARSH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-3006595-G-A is Benign according to our data. Variant chrX-3006595-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3349104.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSH	NM_001011719.2 link	c.-18G>A		5_prime_UTR_variant	Exon 1 of 9	ENST00000381130.3	NP_001011719.1	Q5FYA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSH	ENST00000381130 link	c.-18G>A		5_prime_UTR_variant	Exon 1 of 9	1	NM_001011719.2	ENSP00000370522.3		Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.000242

AC:

AN:

111666

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

33872

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000955

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000357

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000189

AC:

AN:

180348

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

64880

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.0000747

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000628

Gnomad NFE exome

AF:

0.000346

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.000675

AC:

730

AN:

1082160

Hom.:

Cov.:

AF XY:

0.000625

AC XY:

218

AN XY:

348996

show subpopulations

Gnomad4 AFR exome

AF:

0.000192

Gnomad4 AMR exome

AF:

0.0000572

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000862

Gnomad4 OTH exome

AF:

0.000175

GnomAD4 genome

AF:

0.000242

AC:

AN:

111717

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

33933

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.0000954

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000357

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000654

Hom.:

Bravo

AF:

0.000295

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARSH-related condition

Benign:1

Sep 09, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.5

DANN

Benign

0.47

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over