rs1554126383

Variant names:

• chr5-150302261-T-A
• rs1554126383
• NM_001012301.4:c.113A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012301.4(ARSI):​c.113A>T​(p.Gln38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARSI NM_001012301.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.119
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104741484).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012301.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSI	NM_001012301.4	MANE Select	c.113A>T	p.Gln38Leu	missense	Exon 1 of 2	NP_001012301.1	Q5FYB1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSI	ENST00000328668.8	TSL:1 MANE Select	c.113A>T	p.Gln38Leu	missense	Exon 1 of 2	ENSP00000333395.7	Q5FYB1-1
	ARSI	ENST00000515301.2	TSL:4	c.-118-3649A>T		intron	N/A	ENSP00000426879.2	Q5FYB1-2
	ARSI	ENST00000509146.1	TSL:4	c.-118-3649A>T		intron	N/A	ENSP00000420955.1	D6RDH0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.35	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.10	T
MetaSVM	Uncertain	0.034	D
MutationAssessor	Benign	1.1	L
PhyloP100		0.12
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.93	N
REVEL	Uncertain	0.35
Sift	Benign	0.19	T
Sift4G	Benign	0.23	T
Polyphen		0.0010	B
Vest4		0.072
MutPred		0.22		Gain of stability (P = 0.0894)
MVP		0.75
MPC		0.26
ClinPred		0.076	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.10
gMVP		0.44
Mutation Taster		=96/4	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

Other links and lift over

dbSNP: rs1554126383; hg19: chr5-149681824;