rs77196282

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001012301.4(ARSI):c.91G>T(p.Gly31Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,605,262 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 37 hom. )

Consequence

ARSI
NM_001012301.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive spastic paraplegia type 66
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ARSI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023495257).

BP6

Variant 5-150302283-C-A is Benign according to our data. Variant chr5-150302283-C-A is described in ClinVar as [Benign]. Clinvar id is 465200.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0131 (1995/152230) while in subpopulation AFR AF = 0.0456 (1895/41558). AF 95% confidence interval is 0.0439. There are 50 homozygotes in GnomAd4. There are 936 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4 link	c.91G>T	p.Gly31Trp	missense_variant	Exon 1 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.91G>T	p.Gly31Trp	missense_variant	Exon 1 of 2	1	NM_001012301.4	ENSP00000333395.7	Q5FYB1-1
ARSI	ENST00000515301.2 link	c.-118-3671G>T		intron_variant	Intron 1 of 1	4		ENSP00000426879.2	Q5FYB1-2
ARSI	ENST00000509146.1 link	c.-118-3671G>T		intron_variant	Intron 1 of 1	4		ENSP00000420955.1	D6RDH0

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1990

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0456

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

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:

0.000176

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00318

AC:

717

AN:

225804

AF XY:

0.00237

show subpopulations

Gnomad AFR exome

AF:

0.0469

Gnomad AMR exome

AF:

0.00210

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.000902

GnomAD4 exome

AF:

0.00133

AC:

1936

AN:

1453032

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

787

AN XY:

722254

show subpopulations

African (AFR)

AF:

0.0464

AC:

1545

AN:

33280

American (AMR)

AF:

0.00233

AC:

101

AN:

43336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25796

East Asian (EAS)

AF:

0.00

AC:

AN:

39468

South Asian (SAS)

AF:

0.0000706

AC:

AN:

84992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51530

Middle Eastern (MID)

AF:

0.00192

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.0000821

AC:

AN:

1108908

Other (OTH)

AF:

0.00303

AC:

182

AN:

59992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

101

202

303

404

505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0131

AC:

1995

AN:

152230

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

936

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0456

AC:

1895

AN:

41558

American (AMR)

AF:

0.00431

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67988

Other (OTH)

AF:

0.0104

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

104

208

312

416

520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.0151

ESP6500AA

AF:

0.0342

AC:

150

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00347

AC:

417

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spastic paraplegia

Benign:1

Nov 26, 2024

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

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.21

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0023

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

1.4

PhyloP100

1.4

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.36

Sift

Benign

0.18

Sift4G

Uncertain

0.0050

Polyphen

0.94

Vest4

0.17

MVP

0.61

MPC

0.60

ClinPred

0.013

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.36

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs77196282

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over