Variant X-2907624-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_001669.4(ARSD):c.1429G>A(p.Val477Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,102,424 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000034 ( 0 hom. 9 hem. )

Consequence

ARSD
NM_001669.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.22

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027947545).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARSD	NM_001669.4 linkuse as main transcript	c.1429G>A	p.Val477Ile	missense_variant	10/10	ENST00000381154.6	NP_001660.2
ARSD	XM_005274514.3 linkuse as main transcript	c.1294G>A	p.Val432Ile	missense_variant	9/9		XP_005274571.1
ARSD	XM_047442108.1 linkuse as main transcript	c.1291G>A	p.Val431Ile	missense_variant	10/10		XP_047298064.1
ARSD	XM_005274515.3 linkuse as main transcript	c.*353G>A		3_prime_UTR_variant	10/10		XP_005274572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSD	ENST00000381154.6 linkuse as main transcript	c.1429G>A	p.Val477Ile	missense_variant	10/10	1	NM_001669.4	ENSP00000370546	P1	P51689-1
ARSD	ENST00000458014.1 linkuse as main transcript	c.235G>A	p.Val79Ile	missense_variant	3/4	3		ENSP00000409180
ARSD	ENST00000495294.1 linkuse as main transcript	n.564G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

112973

Hom.:

Cov.:

AF XY:

0.0000854

AC XY:

AN XY:

35117

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00140

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000601

AC:

AN:

66511

Hom.:

AF XY:

0.0000635

AC XY:

AN XY:

15749

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000452

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000344

AC:

AN:

989402

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

311524

show subpopulations

Gnomad4 AFR exome

AF:

0.000132

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000744

Gnomad4 SAS exome

AF:

0.0000750

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000761

Gnomad4 OTH exome

AF:

0.0000483

GnomAD4 genome

AF:

0.000106

AC:

AN:

113022

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

35176

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00140

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.000264

AC:

ESP6500EA

AF:

0.000150

AC:

ExAC

AF:

0.000105

AC:

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

Jun 07, 2023

The c.1429G>A (p.V477I) alteration is located in exon 10 (coding exon 10) of the ARSD gene. This alteration results from a G to A substitution at nucleotide position 1429, causing the valine (V) at amino acid position 477 to be replaced by an isoleucine (I). 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

0.072

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.47

DANN

Benign

0.94

DEOGEN2

Benign

0.34

T;.

FATHMM_MKL

Benign

0.0099

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

0.94

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.11

Sift

Benign

0.46

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.20

B;.

Vest4

0.034

MVP

0.50

MPC

0.14

ClinPred

0.0089

GERP RS

-2.9

Varity_R

0.048

gMVP

0.17

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