rs200459738

Variant names:

• chr4-113903236-C-A
• NM_024590.4:c.838G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-113903236-C-A
• chr4-113903236-C-G
• chr4-113903236-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024590.4(ARSJ):​c.838G>T​(p.Glu280*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARSJ NM_024590.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.09

Genes affected

ARSJ (HGNC:26286): (arylsulfatase family member J) Sulfatases (EC 3.1.5.6), such as ARSJ, hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005 [PubMed 16174644]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSJ	NM_024590.4	c.838G>T	p.Glu280*	stop_gained	Exon 2 of 2	ENST00000315366.8	NP_078866.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSJ	ENST00000315366.8	c.838G>T	p.Glu280*	stop_gained	Exon 2 of 2	1	NM_024590.4	ENSP00000320219.7
ARSJ	ENST00000509829.1	n.*517G>T		non_coding_transcript_exon_variant	Exon 4 of 4	1		ENSP00000421327.1
ARSJ	ENST00000509829.1	n.*517G>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000421327.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727234

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
Vest4		0.31
GERP RS		3.9

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: chr4-114824392;