4-113902830-C-T

Variant names:

• chr4-113902830-C-T
• rs75252202
• NM_024590.4:c.1244G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BP4_Moderate BP6_Moderate BS2

The NM_024590.4(ARSJ):​c.1244G>A​(p.Arg415Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,614,062 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (8 hom.)
• Consequence: ARSJ NM_024590.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.81
• Publications: 6 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: Benign. The variant received -7 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 10: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, phyloP100way_vertebrate, REVEL, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.13607109).
• BP6: Variant 4-113902830-C-T is Benign according to our data. Variant chr4-113902830-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 730947.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

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.1244G>A	p.Arg415Gln	missense	Exon 2 of 2	NP_078866.3
	ARSJ	NM_001354210.2		c.1244G>A	p.Arg415Gln	missense	Exon 2 of 3	NP_001341139.1
	ARSJ	NM_001354211.2		c.896G>A	p.Arg299Gln	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.1244G>A	p.Arg415Gln	missense	Exon 2 of 2	ENSP00000320219.7	Q5FYB0
	ARSJ	ENST00000509829.1	TSL:1	n.*923G>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000421327.1	D6RGC1
	ARSJ	ENST00000509829.1	TSL:1	n.*923G>A		3_prime_UTR	Exon 4 of 4	ENSP00000421327.1	D6RGC1

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 152062 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00235

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00170 AC: 423 AN: 249528 AF XY: 0.00174

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.000278

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00283

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.00229 AC: 3345 AN: 1461882 Hom.: 8 Cov.: 32 AF XY: 0.00227 AC XY: 1650 AN XY: 727242

African (AFR) AF: 0.000358 AC: 12 AN: 33480

American (AMR) AF: 0.000268 AC: 12 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000842 AC: 22 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00145 AC: 125 AN: 86254

European-Finnish (FIN) AF: 0.00161 AC: 86 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00266 AC: 2961 AN: 1112010

Other (OTH) AF: 0.00202 AC: 122 AN: 60396

GnomAD4 genome AF: 0.00135 AC: 205 AN: 152180 Hom.: 1 Cov.: 32 AF XY: 0.00130 AC XY: 97 AN XY: 74412

African (AFR) AF: 0.000361 AC: 15 AN: 41494

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4810

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00235 AC: 160 AN: 68008

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00182 Hom.: 2

Bravo AF: 0.00125

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000258 AC: 1

ESP6500EA AF: 0.00205 AC: 17

ExAC AF: 0.00187 AC: 226

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00219

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.14	T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.88
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.78
MVP		0.98
MPC		1.2
ClinPred		0.058	T
GERP RS		5.6
Varity_R		0.42
gMVP		0.95
Mutation Taster		=93/7	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: rs75252202; hg19: chr4-114823986; COSMIC: COSV59539353; COSMIC: COSV59539353;