Genetic Variant ARSI:c.*480C>A (chr5-150296734-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001012301.4(ARSI):c.*480C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 153,632 control chromosomes in the GnomAD database, including 887 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 884 hom., cov: 33)

Exomes 𝑓: 0.050 ( 3 hom. )

Consequence

ARSI
NM_001012301.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.167

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4 link	c.*480C>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000328668.8	NP_001012301.1	Q5FYB1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSI	ENST00000328668.8 link	c.*480C>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001012301.4	ENSP00000333395.7		Q5FYB1-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15359

AN:

152134

Hom.:

883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.0722

Gnomad ASJ

AF:

0.0553

Gnomad EAS

AF:

0.0365

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.0845

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0931

Gnomad OTH

AF:

0.113

GnomAD4 exome

AF:

0.0500

AC:

AN:

1380

Hom.:

Cov.:

AF XY:

0.0567

AC XY:

AN XY:

776

show subpopulations

African (AFR)

AF:

0.0909

AC:

AN:

American (AMR)

AF:

0.00893

AC:

AN:

112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.143

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0545

AC:

AN:

1100

Other (OTH)

AF:

0.0370

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.101

AC:

15380

AN:

152252

Hom.:

884

Cov.:

AF XY:

0.0984

AC XY:

7322

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.148

AC:

6131

AN:

41550

American (AMR)

AF:

0.0721

AC:

1103

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0553

AC:

192

AN:

3472

East Asian (EAS)

AF:

0.0364

AC:

188

AN:

5166

South Asian (SAS)

AF:

0.0321

AC:

155

AN:

4830

European-Finnish (FIN)

AF:

0.0845

AC:

897

AN:

10612

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0931

AC:

6329

AN:

68000

Other (OTH)

AF:

0.111

AC:

235

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

702

1404

2106

2808

3510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0855

Hom.:

434

Bravo

AF:

0.103

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.59

(source)

DANN

Benign

0.39

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over