4-113902920-A-G

Variant names:

• chr4-113902920-A-G
• NM_024590.4:c.1154T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024590.4(ARSJ):​c.1154T>C​(p.Ile385Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARSJ NM_024590.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.20
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024590.4. 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
	ARSJ	NM_024590.4	MANE Select	c.1154T>C	p.Ile385Thr	missense	Exon 2 of 2	NP_078866.3
	ARSJ	NM_001354210.2		c.1154T>C	p.Ile385Thr	missense	Exon 2 of 3	NP_001341139.1
	ARSJ	NM_001354211.2		c.806T>C	p.Ile269Thr	missense	Exon 6 of 7	NP_001341140.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSJ	ENST00000315366.8	TSL:1 MANE Select	c.1154T>C	p.Ile385Thr	missense	Exon 2 of 2	ENSP00000320219.7	Q5FYB0
	ARSJ	ENST00000509829.1	TSL:1	n.*833T>C		non_coding_transcript_exon	Exon 4 of 4	ENSP00000421327.1	D6RGC1
	ARSJ	ENST00000509829.1	TSL:1	n.*833T>C		3_prime_UTR	Exon 4 of 4	ENSP00000421327.1	D6RGC1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.80	D
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Benign	0.85	L
PhyloP100		9.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.2	D
REVEL	Pathogenic	0.68
Sift	Benign	0.10	T
Sift4G	Benign	0.097	T
Polyphen		0.39	B
Vest4		0.48
MutPred		0.72		Gain of disorder (P = 0.0486)
MVP		0.81
MPC		0.69
ClinPred		0.84	D
GERP RS		5.6
Varity_R		0.21
gMVP		0.79
Mutation Taster		=51/49	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

hg19: chr4-114824076;