X-2909889-C-T

Position:

chrX-2909889-C-T

Variant summary

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

The ENST00000381154.6(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. 14/19 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
ENST00000381154.6 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:

ARSD (HGNC:):

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=0.0035035014).

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 male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.00886

AC:

977

AN:

110295

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

225

AN XY:

32497

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

GnomAD3 exomes

AF:

0.00249

AC:

455

AN:

182712

Hom.:

AF XY:

0.00141

AC XY:

AN XY:

67322

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 SAS exome

AF:

0.0000525

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

Gnomad4 AMR exome

AF:

0.00207

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000807

Gnomad4 OTH exome

AF:

0.00221

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

Gnomad4 AMR

AF:

0.00609

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000948

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00279

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

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;.

MutationTaster

Benign

1.0

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

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