Variant X-3006652-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001011719.2(ARSH):c.40G>A(p.Ala14Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 1,209,307 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 120 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00034 ( 0 hom. 114 hem. )

Consequence

ARSH
NM_001011719.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.05

Variant links:

Genes affected

ARSH (HGNC:32488): (arylsulfatase family member H) Sulfatases, such as ARSH, hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005 [PubMed 16174644]).[supplied by OMIM, Mar 2008]

ARSH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSH	NM_001011719.2 link	c.40G>A	p.Ala14Thr	missense_variant	Exon 1 of 9	ENST00000381130.3	NP_001011719.1	Q5FYA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSH	ENST00000381130.3 link	c.40G>A	p.Ala14Thr	missense_variant	Exon 1 of 9	1	NM_001011719.2	ENSP00000370522.3		Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

111338

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

33516

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000339

Gnomad OTH

AF:

0.000669

GnomAD3 exomes

AF:

0.000147

AC:

AN:

183166

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

67606

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000330

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000338

AC:

371

AN:

1097917

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

114

AN XY:

363279

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:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000406

Gnomad4 OTH exome

AF:

0.000608

GnomAD4 genome

AF:

0.000171

AC:

AN:

111390

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

33578

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000339

Gnomad4 OTH

AF:

0.000661

Alfa

AF:

0.000243

Hom.:

Bravo

AF:

0.000140

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000297

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.40G>A (p.A14T) alteration is located in exon 1 (coding exon 1) of the ARSH gene. This alteration results from a G to A substitution at nucleotide position 40, causing the alanine (A) at amino acid position 14 to be replaced by a threonine (T). 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

0.19

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.44

MetaSVM

Pathogenic

0.97

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.52

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.44

MVP

0.57

MPC

0.62

ClinPred

0.35

GERP RS

1.8

Varity_R

0.52

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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