Variant 4-113902830-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3BP4_ModerateBP6_ModerateBS2

The NM_024590.4(ARSJ):c.1244G>A(p.Arg415Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,614,062 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 8 hom. )

Consequence

ARSJ
NM_024590.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.81

Variant links:

Genes affected

ARSJ (HGNC:26286): (arylsulfatase family member J) Sulfatases (EC 3.1.5.6), such as ARSJ, 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]

ARSJ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, phyloP100way_vertebrate, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.13607109).

BP6

Variant 4-113902830-C-T is Benign according to our data. Variant chr4-113902830-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 730947.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSJ	NM_024590.4 linkuse as main transcript	c.1244G>A	p.Arg415Gln	missense_variant	2/2	ENST00000315366.8	NP_078866.3	Q5FYB0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARSJ	ENST00000315366.8 linkuse as main transcript	c.1244G>A	p.Arg415Gln	missense_variant	2/2	1	NM_024590.4	ENSP00000320219.7	Q5FYB0
ARSJ	ENST00000509829.1 linkuse as main transcript	n.*923G>A		non_coding_transcript_exon_variant	4/4	1		ENSP00000421327.1	D6RGC1
ARSJ	ENST00000509829.1 linkuse as main transcript	n.*923G>A		3_prime_UTR_variant	4/4	1		ENSP00000421327.1	D6RGC1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00235

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00170

AC:

423

AN:

249528

Hom.:

AF XY:

0.00174

AC XY:

236

AN XY:

135372

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00283

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.00229

AC:

3345

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

1650

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.00161

Gnomad4 NFE exome

AF:

0.00266

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152180

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00235

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.00125

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000258

AC:

ESP6500EA

AF:

0.00205

AC:

ExAC

AF:

0.00187

AC:

226

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00191

EpiControl

AF:

0.00219

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.56

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.14

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.2

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-4.0

REVEL

Pathogenic

0.88

Sift

Uncertain

0.013

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.78

MVP

0.98

MPC

1.2

ClinPred

0.058

GERP RS

5.6

Varity_R

0.42

gMVP

0.95

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