rs200012526

Positions:

• chr5-150302287-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001012301.4(ARSI):​c.87C>T​(p.Ala29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,604,888 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (22 hom.)
• Consequence: ARSI NM_001012301.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.931

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 5-150302287-G-A is Benign according to our data. Variant chr5-150302287-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.931 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSI	NM_001012301.4	c.87C>T	p.Ala29=	synonymous_variant	1/2	ENST00000328668.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSI	ENST00000328668.8	c.87C>T	p.Ala29=	synonymous_variant	1/2	1	NM_001012301.4	P1
ARSI	ENST00000509146.1	c.-118-3675C>T		intron_variant		4
ARSI	ENST00000515301.2	c.-118-3675C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 540 AN: 152142 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00471

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00334 AC: 753 AN: 225664 Hom.: 2 AF XY: 0.00326 AC XY: 402 AN XY: 123364

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.00618

Gnomad ASJ exome AF: 0.000108

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000455

Gnomad NFE exome AF: 0.00492

Gnomad OTH exome AF: 0.00398

GnomAD4 exome AF: 0.00448 AC: 6508 AN: 1452630 Hom.: 22 Cov.: 31 AF XY: 0.00436 AC XY: 3145 AN XY: 722044

Gnomad4 AFR exome AF: 0.00207

Gnomad4 AMR exome AF: 0.00599

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000466

Gnomad4 NFE exome AF: 0.00537

Gnomad4 OTH exome AF: 0.00327

GnomAD4 genome AF: 0.00355 AC: 540 AN: 152258 Hom.: 3 Cov.: 32 AF XY: 0.00325 AC XY: 242 AN XY: 74428

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00471

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00358 Hom.: 0

Bravo AF: 0.00421

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

ARSI: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.9
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Other links and lift over

dbSNP: rs200012526; hg19: chr5-149681850;