X-3080945-G-C

Variant names:

• chrX-3080945-G-C
• rs965998855
• NM_001201539.2:c.338G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001201539.2(ARSF):​c.338G>C​(p.Gly113Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ARSF NM_001201539.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.35
• Publications: 0 publications found

Genes affected

ARSF (HGNC:721): (arylsulfatase F) This gene is a member of the sulfatase family, and more specifically, the arylsulfatase subfamily. Members of the subfamily share similarity in sequence and splice sites, and are clustered together on chromosome X, suggesting that they are derived from recent gene duplication events. Sulfatases are essential for the correct composition of bone and cartilage matrix. The activity of this protein, unlike that of arylsulfatase E, is not inhibited by warfarin. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201539.2. 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
	ARSF	NM_001201539.2	MANE Select	c.338G>C	p.Gly113Ala	missense	Exon 5 of 11	NP_001188468.1	P54793
	ARSF	NM_001201538.2		c.338G>C	p.Gly113Ala	missense	Exon 5 of 11	NP_001188467.1	P54793
	ARSF	NM_004042.5		c.338G>C	p.Gly113Ala	missense	Exon 5 of 11	NP_004033.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSF	ENST00000381127.6	TSL:1 MANE Select	c.338G>C	p.Gly113Ala	missense	Exon 5 of 11	ENSP00000370519.1	P54793
	ARSF	ENST00000359361.2	TSL:1	c.338G>C	p.Gly113Ala	missense	Exon 5 of 11	ENSP00000352319.2	P54793
	ARSF	ENST00000886821.1		c.338G>C	p.Gly113Ala	missense	Exon 5 of 11	ENSP00000556880.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	ARSF-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.73	D
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.3
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.58		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.46
MPC		0.48
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.91
gMVP		0.64
Mutation Taster		=86/14	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: rs965998855; hg19: chrX-2998986;