Variant X-3010084-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.24

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 -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 id is 558976.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-3010084-C-T is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSH	NM_001011719.2 linkuse as main transcript	c.147C>T	p.Leu49Leu	synonymous_variant	2/9	ENST00000381130.3	NP_001011719.1	Q5FYA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSH	ENST00000381130.3 linkuse as main transcript	c.147C>T	p.Leu49Leu	synonymous_variant	2/9	1	NM_001011719.2	ENSP00000370522.3		Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.0452

AC:

5037

AN:

111542

Hom.:

116

Cov.:

AF XY:

0.0424

AC XY:

1430

AN XY:

33708

show subpopulations

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

GnomAD3 exomes

AF:

0.0466

AC:

8538

AN:

183277

Hom.:

177

AF XY:

0.0486

AC XY:

3291

AN XY:

67721

show subpopulations

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 SAS exome

AF:

0.0362

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.:

AF XY:

0.0621

AC XY:

22540

AN XY:

362945

show subpopulations

Gnomad4 AFR exome

AF:

0.0126

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.0574

Gnomad4 EAS exome

AF:

0.00629

Gnomad4 SAS exome

AF:

0.0361

Gnomad4 FIN exome

AF:

0.0676

Gnomad4 NFE exome

AF:

0.0696

Gnomad4 OTH exome

AF:

0.0579

GnomAD4 genome

AF:

0.0451

AC:

5034

AN:

111598

Hom.:

116

Cov.:

AF XY:

0.0423

AC XY:

1430

AN XY:

33774

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.0243

Gnomad4 ASJ

AF:

0.0541

Gnomad4 EAS

AF:

0.0101

Gnomad4 SAS

AF:

0.0267

Gnomad4 FIN

AF:

0.0629

Gnomad4 NFE

AF:

0.0683

Gnomad4 OTH

AF:

0.0433

Alfa

AF:

0.0598

Hom.:

487

Bravo

AF:

0.0406

EpiCase

AF:

0.0635

EpiControl

AF:

0.0649

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	May 10, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.29

DANN

Benign

0.53

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

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