rs965998855

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-3080945-G-A
• chrX-3080945-G-C
• chrX-3080945-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_001201539.2(ARSF):​c.338G>A​(p.Gly113Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000546 in 1,097,942 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000055 (0 hom. 3 hem.)
• Consequence: ARSF NM_001201539.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.915
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSF	NM_001201539.2	c.338G>A	p.Gly113Asp	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>A	p.Gly113Asp	missense_variant	Exon 5 of 11	1	NM_001201539.2	ENSP00000370519.1
ARSF	ENST00000359361.2	c.338G>A	p.Gly113Asp	missense_variant	Exon 5 of 11	1		ENSP00000352319.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000546 AC: 6 AN: 1097942 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 3 AN XY: 363300

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000713

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.36
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D;D
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.79	.;T
M_CAP	Pathogenic	0.58	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-6.4	D;D
REVEL	Pathogenic	0.72
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.66
MutPred		0.49		Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);
MVP		0.59
MPC		0.56
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.93
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-2998986; COSMIC: COSV100839460;