rs139203947

chr5-150298072-G-Achr5-150298072-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001012301.4(ARSI):c.852C>T(p.Tyr284=) 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.17

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 -13 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSI	NM_001012301.4	c.852C>T	p.Tyr284=	synonymous_variant	2/2	ENST00000328668.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSI	ENST00000328668.8	c.852C>T	p.Tyr284=	synonymous_variant	2/2	1	NM_001012301.4	P1
ARSI	ENST00000515301.2	c.423C>T	p.Tyr141=	synonymous_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.000803 AC: 122 AN: 152004 Hom.: 0 Cov.: 32

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

GnomAD3 exomes AF: 0.000749 AC: 187 AN: 249676 Hom.: 0 AF XY: 0.000791 AC XY: 107 AN XY: 135298

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 SAS 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

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.00390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000571

Gnomad4 NFE exome AF: 0.000950

Gnomad4 OTH exome AF: 0.000695

GnomAD4 genome AF: 0.000802 AC: 122 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.000820 AC XY: 61 AN XY: 74354

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.000916

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00126

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.000998 Hom.: 0

Bravo AF: 0.000850

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spastic paraplegia Benign:1

Likely 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	-0.67
Cadd	Benign	0.33
Dann	Benign	0.67

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: rs139203947; hg19: chr5-149677635;