chrX-2909889-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001669.4(ARSD):c.1226G>A(p.Gly409Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,208,460 control chromosomes in the GnomAD database, including 28 homozygotes. There are 522 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 13 hom., 226 hem., cov: 22)

Exomes 𝑓: 0.0010 ( 15 hom. 296 hem. )

Consequence

ARSD
NM_001669.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.09

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035035014).

BP6

Variant X-2909889-C-T is Benign according to our data. Variant chrX-2909889-C-T is described in ClinVar as [Benign]. Clinvar id is 787153.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 = 0.00889 (981/110337) while in subpopulation AFR AF = 0.0296 (900/30355). AF 95% confidence interval is 0.028. There are 13 homozygotes in GnomAd4. There are 226 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSD	NM_001669.4 link	c.1226G>A	p.Gly409Glu	missense_variant	Exon 8 of 10	ENST00000381154.6	NP_001660.2	P51689-1A0A140VK06
ARSD	XM_005274514.3 link	c.1091G>A	p.Gly364Glu	missense_variant	Exon 7 of 9		XP_005274571.1
ARSD	XM_047442108.1 link	c.1088G>A	p.Gly363Glu	missense_variant	Exon 8 of 10		XP_047298064.1
ARSD	XM_005274515.3 link	c.1226G>A	p.Gly409Glu	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.1226G>A	p.Gly409Glu	missense_variant	Exon 8 of 10	1	NM_001669.4	ENSP00000370546.1	P51689-1
ARSD	ENST00000458014.1 link	c.32G>A	p.Gly11Glu	missense_variant	Exon 1 of 4	3		ENSP00000409180.1	H7C327
ARSD	ENST00000495294.1 link	n.119-1084G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00886

AC:

977

AN:

110295

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.0000947

Gnomad OTH

AF:

0.00815

GnomAD2 exomes

AF:

0.00249

AC:

455

AN:

182712

AF XY:

0.00141

show subpopulations

Gnomad AFR exome

AF:

0.0301

Gnomad AMR exome

AF:

0.00172

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000614

Gnomad OTH exome

AF:

0.00177

GnomAD4 exome

AF:

0.00101

AC:

1106

AN:

1098123

Hom.:

Cov.:

AF XY:

0.000814

AC XY:

296

AN XY:

363491

show subpopulations

Gnomad4 AFR exome

AF:

0.0322

AC:

851

AN:

26397

Gnomad4 AMR exome

AF:

0.00207

AC:

AN:

35199

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

19385

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

30199

Gnomad4 SAS exome

AF:

0.000111

AC:

AN:

54137

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

40474

Gnomad4 NFE exome

AF:

0.0000807

AC:

AN:

842107

Gnomad4 Remaining exome

AF:

0.00221

AC:

102

AN:

46089

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00889

AC:

981

AN:

110337

Hom.:

Cov.:

AF XY:

0.00694

AC XY:

226

AN XY:

32549

show subpopulations

Gnomad4 AFR

AF:

0.0296

AC:

0.0296492

AN:

0.0296492

Gnomad4 AMR

AF:

0.00609

AC:

0.00608696

AN:

0.00608696

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000948

AC:

0.0000947562

AN:

0.0000947562

Gnomad4 OTH

AF:

0.00804

AC:

0.0080429

AN:

0.0080429

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00270

Hom.:

Bravo

AF:

0.0108

ESP6500AA

AF:

0.0292

AC:

112

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00275

AC:

334

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.20

DANN

Benign

0.75

DEOGEN2

Benign

0.37

T;.

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.24

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

-0.92

N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

2.0

N;N

REVEL

Benign

0.21

Sift

Benign

0.36

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0

B;.

Vest4

0.17

MVP

0.97

MPC

0.20

ClinPred

0.0052

GERP RS

-0.25

Varity_R

0.045

gMVP

0.69

Mutation Taster

=100/0

polymorphism (auto)

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