Variant rs746453494 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001669.4(ARSD):c.1180G>T(p.Gly394Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000907 in 110,287 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 22)

Consequence

ARSD
NM_001669.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.64

Variant links:

Genes affected

ARSD (HGNC:717): (arylsulfatase D) The protein encoded by this gene is a member of the sulfatase family. Sulfatases are essential for the correct composition of bone and cartilage matrix. The encoded protein is postranslationally glycosylated and localized to the lysosome. This gene is located within a cluster of similar arylsulfatase genes on chromosome X. A related pseudogene has been identified in the pseudoautosomal region of chromosome Y. [provided by RefSeq, Jul 2011]

ARSD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSD	NM_001669.4 link	c.1180G>T	p.Gly394Trp	missense_variant	Exon 8 of 10	ENST00000381154.6	NP_001660.2	P51689-1A0A140VK06
ARSD	XM_005274514.3 link	c.1045G>T	p.Gly349Trp	missense_variant	Exon 7 of 9		XP_005274571.1
ARSD	XM_047442108.1 link	c.1042G>T	p.Gly348Trp	missense_variant	Exon 8 of 10		XP_047298064.1
ARSD	XM_005274515.3 link	c.1180G>T	p.Gly394Trp	missense_variant	Exon 8 of 10		XP_005274572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARSD	ENST00000381154.6 link	c.1180G>T	p.Gly394Trp	missense_variant	Exon 8 of 10	1	NM_001669.4	ENSP00000370546.1	P51689-1
ARSD	ENST00000495294.1 link	n.119-1130G>T		intron_variant	Intron 1 of 2	2
ARSD	ENST00000458014.1 link	c.-15G>T		upstream_gene_variant		3		ENSP00000409180.1	H7C327

Frequencies

GnomAD3 genomes

AF:

0.00000907

AC:

AN:

110287

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32495

show subpopulations

Gnomad AFR

AF:

0.0000330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000907

AC:

AN:

110287

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32495

show subpopulations

Gnomad4 AFR

AF:

0.0000330

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.89

MetaRNN

Pathogenic

0.97

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-7.7

REVEL

Pathogenic

0.66

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.74

MutPred

0.67

Gain of catalytic residue at G394 (P = 0.0369);

MVP

0.92

MPC

0.72

ClinPred

0.97

GERP RS

3.0

Varity_R

0.63

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over