Variant X-2909935-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2

The ENST00000381154.6(ARSD):c.1180G>A(p.Gly394Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000612 in 1,208,388 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000062 ( 0 hom. 18 hem. )

Consequence

ARSD
ENST00000381154.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

ARSD (HGNC:):

ARSD links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.987

BS2

High Hemizygotes in GnomAdExome4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSD	NM_001669.4 linkuse as main transcript	c.1180G>A	p.Gly394Arg	missense_variant	8/10	ENST00000381154.6	NP_001660.2	P51689-1A0A140VK06
ARSD	XM_005274514.3 linkuse as main transcript	c.1045G>A	p.Gly349Arg	missense_variant	7/9		XP_005274571.1
ARSD	XM_047442108.1 linkuse as main transcript	c.1042G>A	p.Gly348Arg	missense_variant	8/10		XP_047298064.1
ARSD	XM_005274515.3 linkuse as main transcript	c.1180G>A	p.Gly394Arg	missense_variant	8/10		XP_005274572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARSD	ENST00000381154.6 linkuse as main transcript	c.1180G>A	p.Gly394Arg	missense_variant	8/10	1	NM_001669.4	ENSP00000370546.1	P51689-1
ARSD	ENST00000495294.1 linkuse as main transcript	n.119-1130G>A		intron_variant		2
ARSD	ENST00000458014.1 linkuse as main transcript	c.-15G>A		upstream_gene_variant		3		ENSP00000409180.1	H7C327

Frequencies

GnomAD3 genomes

AF:

0.0000544

AC:

AN:

110287

Hom.:

Cov.:

AF XY:

0.0000308

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:

0.0000947

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000219

AC:

AN:

182595

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

67231

show subpopulations

Gnomad AFR exome

AF:

0.0000764

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000369

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000619

AC:

AN:

1098101

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

363475

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000784

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000544

AC:

AN:

110287

Hom.:

Cov.:

AF XY:

0.0000308

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:

0.0000947

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000145

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Feb 28, 2024

The c.1180G>A (p.G394R) alteration is located in exon 8 (coding exon 8) of the ARSD gene. This alteration results from a G to A substitution at nucleotide position 1180, causing the glycine (G) at amino acid position 394 to be replaced by an arginine (R). 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

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.84

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-7.7

REVEL

Pathogenic

0.77

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.83

MutPred

0.90

Gain of MoRF binding (P = 0.0075);

MVP

0.96

MPC

0.72

ClinPred

0.92

GERP RS

3.0

Varity_R

0.81

gMVP

0.98

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