X-3080945-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_001201539.2(ARSF):​c.338G>T​(p.Gly113Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,942 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G113A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
• Consequence: ARSF NM_001201539.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.939
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

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>T	p.Gly113Val	missense	Exon 5 of 11	NP_001188468.1	P54793
	ARSF	NM_001201538.2		c.338G>T	p.Gly113Val	missense	Exon 5 of 11	NP_001188467.1	P54793
	ARSF	NM_004042.5		c.338G>T	p.Gly113Val	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>T	p.Gly113Val	missense	Exon 5 of 11	ENSP00000370519.1	P54793
	ARSF	ENST00000359361.2	TSL:1	c.338G>T	p.Gly113Val	missense	Exon 5 of 11	ENSP00000352319.2	P54793
	ARSF	ENST00000886821.1		c.338G>T	p.Gly113Val	missense	Exon 5 of 11	ENSP00000556880.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097942 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 2 AN XY: 363300

African (AFR) AF: 0.00 AC: 0 AN: 26391

American (AMR) AF: 0.00 AC: 0 AN: 35195

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30193

South Asian (SAS) AF: 0.00 AC: 0 AN: 54111

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841931

Other (OTH) AF: 0.00 AC: 0 AN: 46087

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.3
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-8.3	D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.64		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.82
MPC		0.55
ClinPred		1.0	D
GERP RS		3.4
Varity_R		0.94
gMVP		0.77
Mutation Taster		=83/17	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;