dbSNP rs77878118: ARSI:p.Asn298Asn (chr5-150298030-A-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001012301.4(ARSI):c.894T>C(p.Asn298Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,612,450 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 29 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 149 hom. )

Consequence

ARSI
NM_001012301.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -3.90

Variant links:

Genes affected

ARSI (HGNC:32521): (arylsulfatase family member I) This gene encodes a protein that belongs to a large family of sulfatases that hydrolyze sulfate esters and sulfamates. Members of this family play a role in several cellular processes, including hormone synthesis, cell signaling in development and degradation of macromolecules. The protein encoded by this gene is thought to be secreted, and to function in extracellular space. [provided by RefSeq, Jul 2016]

ARSI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 5-150298030-A-G is Benign according to our data. Variant chr5-150298030-A-G is described in ClinVar as [Benign]. Clinvar id is 465199.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4 link	c.894T>C	p.Asn298Asn	synonymous_variant	Exon 2 of 2	ENST00000328668.8	NP_001012301.1	Q5FYB1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARSI	ENST00000328668.8 link	c.894T>C	p.Asn298Asn	synonymous_variant	Exon 2 of 2	1	NM_001012301.4	ENSP00000333395.7	Q5FYB1-1
ARSI	ENST00000515301.2 link	c.465T>C	p.Asn155Asn	synonymous_variant	Exon 2 of 2	4		ENSP00000426879.2	Q5FYB1-2
ARSI	ENST00000509146.1 link	c.*205T>C		downstream_gene_variant		4		ENSP00000420955.1	D6RDH0

Frequencies

GnomAD3 genomes

AF:

0.00385

AC:

584

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000436

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0915

Gnomad SAS

AF:

0.0121

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00877

AC:

2177

AN:

248288

Hom.:

AF XY:

0.00859

AC XY:

1158

AN XY:

134794

show subpopulations

Gnomad AFR exome

AF:

0.000192

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.00925

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.0000448

Gnomad OTH exome

AF:

0.00459

GnomAD4 exome

AF:

0.00282

AC:

4119

AN:

1460524

Hom.:

149

Cov.:

AF XY:

0.00301

AC XY:

2185

AN XY:

726568

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0696

Gnomad4 SAS exome

AF:

0.00932

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.00813

GnomAD4 genome

AF:

0.00386

AC:

587

AN:

151926

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

317

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.000434

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0914

Gnomad4 SAS

AF:

0.0121

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00618

Alfa

AF:

0.000739

Hom.:

Bravo

AF:

0.00424

Asia WGS

AF:

0.0560

AC:

193

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spastic paraplegia

Benign:1

Jan 17, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ARSI-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.024

DANN

Benign

0.43

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