Variant 4-113902542-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024590.4(ARSJ):c.1532G>A(p.Arg511Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,613,970 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

ARSJ
NM_024590.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.641

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01693967).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSJ	NM_024590.4 linkuse as main transcript	c.1532G>A	p.Arg511Lys	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.1532G>A	p.Arg511Lys	missense_variant	2/2	1	NM_024590.4	ENSP00000320219.7	Q5FYB0
ARSJ	ENST00000509829.1 linkuse as main transcript	n.*1211G>A		non_coding_transcript_exon_variant	4/4	1		ENSP00000421327.1	D6RGC1
ARSJ	ENST00000509829.1 linkuse as main transcript	n.*1211G>A		3_prime_UTR_variant	4/4	1		ENSP00000421327.1	D6RGC1

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000781

AC:

195

AN:

249550

Hom.:

AF XY:

0.000820

AC XY:

111

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.000452

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000557

Gnomad NFE exome

AF:

0.00139

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.00130

AC:

1894

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

924

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00164

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.000835

AC:

127

AN:

152080

Hom.:

Cov.:

AF XY:

0.000781

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.000435

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.000858

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000783

AC:

ESP6500EA

AF:

0.00182

AC:

ExAC

AF:

0.000637

AC:

EpiCase

AF:

0.00153

EpiControl

AF:

0.000948

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.1532G>A (p.R511K) alteration is located in exon 2 (coding exon 2) of the ARSJ gene. This alteration results from a G to A substitution at nucleotide position 1532, causing the arginine (R) at amino acid position 511 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.20

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.50

M_CAP

Benign

0.035

MetaRNN

Benign

0.017

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

-0.13

PrimateAI

Benign

0.42

PROVEAN

Benign

0.55

REVEL

Benign

0.26

Sift

Benign

0.82

Sift4G

Benign

0.69

Polyphen

0.0

Vest4

0.086

MVP

0.87

MPC

0.34

ClinPred

0.0038

GERP RS

4.6

Varity_R

0.071

gMVP

0.62

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