rs77196282

chr5-150302283-C-Achr5-150302283-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001012301.4(ARSI):c.91G>T(p.Gly31Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,605,262 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (37 hom.)
• Consequence: ARSI NM_001012301.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.42

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023495257).
• BP6: Variant 5-150302283-C-A is Benign according to our data. Variant chr5-150302283-C-A is described in ClinVar as [Benign]. Clinvar id is 465200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1995/152230) while in subpopulation AFR AF= 0.0456 (1895/41558). AF 95% confidence interval is 0.0439. There are 50 homozygotes in gnomad4. There are 936 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSI	NM_001012301.4	c.91G>T	p.Gly31Trp	missense_variant	1/2	ENST00000328668.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSI	ENST00000328668.8	c.91G>T	p.Gly31Trp	missense_variant	1/2	1	NM_001012301.4	P1
ARSI	ENST00000509146.1	c.-118-3671G>T		intron_variant		4
ARSI	ENST00000515301.2	c.-118-3671G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1990 AN: 152114 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00318 AC: 717 AN: 225804 Hom.: 8 AF XY: 0.00237 AC XY: 293 AN XY: 123460

Gnomad AFR exome AF: 0.0469

Gnomad AMR exome AF: 0.00210

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.000902

GnomAD4 exome AF: 0.00133 AC: 1936 AN: 1453032 Hom.: 37 Cov.: 31 AF XY: 0.00109 AC XY: 787 AN XY: 722254

Gnomad4 AFR exome AF: 0.0464

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000706

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000821

Gnomad4 OTH exome AF: 0.00303

GnomAD4 genome AF: 0.0131 AC: 1995 AN: 152230 Hom.: 50 Cov.: 32 AF XY: 0.0126 AC XY: 936 AN XY: 74418

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00127 Hom.: 0

Bravo AF: 0.0151

ESP6500AA AF: 0.0342 AC: 150

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.00347 AC: 417

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	21
Dann	Benign	0.83
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0023	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.36
Sift	Benign	0.18	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.94	P
Vest4		0.17
MVP		0.61
MPC		0.60
ClinPred		0.013	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.36

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: rs77196282; hg19: chr5-149681846;