X-3080945-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSF	NM_001201539.2	c.338G>C	p.Gly113Ala	missense_variant	Exon 5 of 11	ENST00000381127.6	NP_001188468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSF	ENST00000381127.6	c.338G>C	p.Gly113Ala	missense_variant	Exon 5 of 11	1	NM_001201539.2	ENSP00000370519.1
ARSF	ENST00000359361.2	c.338G>C	p.Gly113Ala	missense_variant	Exon 5 of 11	1		ENSP00000352319.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

ARSF-related disorder Uncertain:1

Aug 01, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The ARSF c.338G>C variant is predicted to result in the amino acid substitution p.Gly113Ala. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

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;D
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	.;T
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.54
MutPred		0.58		Loss of relative solvent accessibility (P = 0.0676);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

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: rs965998855; hg19: chrX-2998986;