NM_001012301.4:c.852C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001012301.4(ARSI):​c.852C>T​(p.Tyr284Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00084 in 1,613,144 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00084 ( 2 hom. )

Consequence

ARSI
NM_001012301.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.17

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 5-150298072-G-A is Benign according to our data. Variant chr5-150298072-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.17 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARSINM_001012301.4 linkc.852C>T p.Tyr284Tyr synonymous_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
ARSIENST00000328668.8 linkc.852C>T p.Tyr284Tyr synonymous_variant Exon 2 of 2 1 NM_001012301.4 ENSP00000333395.7 Q5FYB1-1
ARSIENST00000515301.2 linkc.423C>T p.Tyr141Tyr synonymous_variant Exon 2 of 2 4 ENSP00000426879.2 Q5FYB1-2
ARSIENST00000509146.1 linkc.*163C>T downstream_gene_variant 4 ENSP00000420955.1 D6RDH0

Frequencies

GnomAD3 genomes
AF:
0.000803
AC:
122
AN:
152004
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000218
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000917
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00126
Gnomad OTH
AF:
0.000480
GnomAD2 exomes
AF:
0.000749
AC:
187
AN:
249676
AF XY:
0.000791
show subpopulations
Gnomad AFR exome
AF:
0.0000623
Gnomad AMR exome
AF:
0.000434
Gnomad ASJ exome
AF:
0.00418
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00109
Gnomad OTH exome
AF:
0.000981
GnomAD4 exome
AF:
0.000844
AC:
1233
AN:
1461022
Hom.:
2
Cov.:
30
AF XY:
0.000821
AC XY:
597
AN XY:
726828
show subpopulations
African (AFR)
AF:
0.000179
AC:
6
AN:
33478
American (AMR)
AF:
0.000447
AC:
20
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00390
AC:
102
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.0000348
AC:
3
AN:
86252
European-Finnish (FIN)
AF:
0.0000571
AC:
3
AN:
52572
Middle Eastern (MID)
AF:
0.000173
AC:
1
AN:
5768
European-Non Finnish (NFE)
AF:
0.000950
AC:
1056
AN:
1112004
Other (OTH)
AF:
0.000695
AC:
42
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.480
Heterozygous variant carriers
0
84
168
253
337
421
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
42
84
126
168
210
<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:
0.000802
AC:
122
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.000820
AC XY:
61
AN XY:
74354
show subpopulations
African (AFR)
AF:
0.000217
AC:
9
AN:
41486
American (AMR)
AF:
0.000916
AC:
14
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00346
AC:
12
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5156
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10588
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00126
AC:
86
AN:
68006
Other (OTH)
AF:
0.000475
AC:
1
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
5
10
16
21
26
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000932
Hom.:
0
Bravo
AF:
0.000850

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jun 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

ARSI: BP4, BP7 -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Spastic paraplegia Benign:1
Dec 04, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
0.33
DANN
Benign
0.67
PhyloP100
-3.2
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs139203947; hg19: chr5-149677635; API