NM_001669.4:c.1498G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001669.4(ARSD):c.1498G>A(p.Val500Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,155,856 control chromosomes in the GnomAD database, including 30 homozygotes. There are 642 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0093 ( 14 hom., 286 hem., cov: 24)

Exomes 𝑓: 0.0012 ( 16 hom. 356 hem. )

Consequence

ARSD
NM_001669.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.70

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005255133).

BP6

Variant X-2907555-C-T is Benign according to our data. Variant chrX-2907555-C-T is described in ClinVar as [Benign]. Clinvar id is 787152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00934 (1055/112968) while in subpopulation AFR AF= 0.0307 (957/31191). AF 95% confidence interval is 0.0291. There are 14 homozygotes in gnomad4. There are 286 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSD	NM_001669.4 link	c.1498G>A	p.Val500Ile	missense_variant	Exon 10 of 10	ENST00000381154.6	NP_001660.2	P51689-1A0A140VK06
ARSD	XM_005274514.3 link	c.1363G>A	p.Val455Ile	missense_variant	Exon 9 of 9		XP_005274571.1
ARSD	XM_047442108.1 link	c.1360G>A	p.Val454Ile	missense_variant	Exon 10 of 10		XP_047298064.1
ARSD	XM_005274515.3 link	c.*422G>A		3_prime_UTR_variant	Exon 10 of 10		XP_005274572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARSD	ENST00000381154.6 link	c.1498G>A	p.Val500Ile	missense_variant	Exon 10 of 10	1	NM_001669.4	ENSP00000370546.1	P51689-1
ARSD	ENST00000458014.1 link	c.304G>A	p.Val102Ile	missense_variant	Exon 3 of 4	3		ENSP00000409180.1	H7C327
ARSD	ENST00000495294.1 link	n.633G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00931

AC:

1051

AN:

112921

Hom.:

Cov.:

AF XY:

0.00813

AC XY:

285

AN XY:

35055

show subpopulations

Gnomad AFR

AF:

0.0306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00631

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000725

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.000225

Gnomad OTH

AF:

0.00988

GnomAD3 exomes

AF:

0.00326

AC:

359

AN:

109976

Hom.:

AF XY:

0.00254

AC XY:

AN XY:

23658

show subpopulations

Gnomad AFR exome

AF:

0.0321

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00259

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000173

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00123

AC:

1278

AN:

1042888

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

356

AN XY:

327542

show subpopulations

Gnomad4 AFR exome

AF:

0.0326

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00202

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000215

Gnomad4 OTH exome

AF:

0.00272

GnomAD4 genome

AF:

0.00934

AC:

1055

AN:

112968

Hom.:

Cov.:

AF XY:

0.00815

AC XY:

286

AN XY:

35112

show subpopulations

Gnomad4 AFR

AF:

0.0307

Gnomad4 AMR

AF:

0.00631

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000727

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000225

Gnomad4 OTH

AF:

0.00977

Alfa

AF:

0.00323

Hom.:

Bravo

AF:

0.0108

ESP6500AA

AF:

0.0278

AC:

106

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00261

AC:

306

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.0010

DANN

Benign

0.75

DEOGEN2

Benign

0.33

T;.

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.087

T;T

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.83

L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

0.20

N;N

REVEL

Benign

0.19

Sift

Benign

0.38

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0010

B;.

Vest4

0.024

MVP

0.62

MPC

0.12

ClinPred

0.0061

GERP RS

-6.1

Varity_R

0.076

gMVP

0.16

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