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GeneBe

rs112583032

chr5-150297541-G-Achr5-150297541-G-Cchr5-150297541-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001012301.4(ARSI):c.1383C>T(p.Ala461=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,613,146 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 29 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 23 hom. )

Consequence

ARSI
NM_001012301.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.23
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-150297541-G-A is Benign according to our data. Variant chr5-150297541-G-A is described in ClinVar as [Benign]. Clinvar id is 533758.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.22 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1594/152334) while in subpopulation AFR AF= 0.034 (1412/41572). AF 95% confidence interval is 0.0325. There are 29 homozygotes in gnomad4. There are 722 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 29 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARSINM_001012301.4 linkuse as main transcriptc.1383C>T p.Ala461= synonymous_variant 2/2 ENST00000328668.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARSIENST00000328668.8 linkuse as main transcriptc.1383C>T p.Ala461= synonymous_variant 2/21 NM_001012301.4 P1Q5FYB1-1
ARSIENST00000515301.2 linkuse as main transcriptc.954C>T p.Ala318= synonymous_variant 2/24 Q5FYB1-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0105
AC:
1593
AN:
152216
Hom.:
29
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0340
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00425
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00147
Gnomad OTH
AF:
0.00764
GnomAD3 exomes
AF:
0.00339
AC:
848
AN:
250276
Hom.:
13
AF XY:
0.00280
AC XY:
379
AN XY:
135320
show subpopulations
Gnomad AFR exome
AF:
0.0350
Gnomad AMR exome
AF:
0.00217
Gnomad ASJ exome
AF:
0.0000995
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.0000472
Gnomad NFE exome
AF:
0.00162
Gnomad OTH exome
AF:
0.00213
GnomAD4 exome
AF:
0.00231
AC:
3380
AN:
1460812
Hom.:
23
Cov.:
29
AF XY:
0.00220
AC XY:
1597
AN XY:
726708
show subpopulations
Gnomad4 AFR exome
AF:
0.0336
Gnomad4 AMR exome
AF:
0.00239
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000186
Gnomad4 FIN exome
AF:
0.000133
Gnomad4 NFE exome
AF:
0.00169
Gnomad4 OTH exome
AF:
0.00349
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0105
AC:
1594
AN:
152334
Hom.:
29
Cov.:
32
AF XY:
0.00969
AC XY:
722
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0340
Gnomad4 AMR
AF:
0.00418
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00147
Gnomad4 OTH
AF:
0.00756
Alfa
AF:
0.00351
Hom.:
6
Bravo
AF:
0.0113
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.00180
EpiControl
AF:
0.00196

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Spastic paraplegia Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 13, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
0.24
Dann
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs112583032; hg19: chr5-149677104; COSMIC: COSV60817052; COSMIC: COSV60817052; API