rs762853375

Variant names:

• chr3-4303398-C-A
• rs762853375
• NM_006515.4:c.28C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-4303398-C-A
• chr3-4303398-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006515.4(SETMAR):​c.28C>A​(p.Arg10Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,407,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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: 0.0000021 (0 hom.)
• Consequence: SETMAR NM_006515.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 0 publications found

Genes affected

SETMAR (HGNC:10762): (SET domain and mariner transposase fusion gene) This gene encodes a fusion protein that contains an N-terminal histone-lysine N-methyltransferase domain and a C-terminal mariner transposase domain. The encoded protein binds DNA and functions in DNA repair activities including non-homologous end joining and double strand break repair. The SET domain portion of this protein specifically methylates histone H3 lysines 4 and 36. This gene exists as a fusion gene only in anthropoid primates, other organisms lack mariner transposase domain. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

SUMF1 Gene-Disease associations (from GenCC):

• mucosulfatidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ENSG00000286579 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-1.47 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006515.4. 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
	SETMAR	NM_006515.4	MANE Select	c.28C>A	p.Arg10Arg	synonymous	Exon 1 of 3	NP_006506.3	Q53H47-1
	SETMAR	NM_001243723.2		c.28C>A	p.Arg10Arg	synonymous	Exon 1 of 4	NP_001230652.1	Q53H47-3
	SETMAR	NM_001320678.2		c.28C>A	p.Arg10Arg	synonymous	Exon 1 of 2	NP_001307607.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETMAR	ENST00000358065.5	TSL:1 MANE Select	c.28C>A	p.Arg10Arg	synonymous	Exon 1 of 3	ENSP00000373354.3	Q53H47-1
	SETMAR	ENST00000430981.1	TSL:1	c.28C>A	p.Arg10Arg	synonymous	Exon 1 of 2	ENSP00000403000.1	Q53H47-2
	SETMAR	ENST00000425046.1	TSL:1	n.28C>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000397463.1	F8WB33

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1407540 Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 2 AN XY: 698624

African (AFR) AF: 0.00 AC: 0 AN: 29366

American (AMR) AF: 0.00 AC: 0 AN: 36550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24864

East Asian (EAS) AF: 0.00 AC: 0 AN: 33132

South Asian (SAS) AF: 0.00 AC: 0 AN: 78376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1088780

Other (OTH) AF: 0.00 AC: 0 AN: 58142

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.4
DANN	Benign	0.59
PhyloP100		-1.5
PromoterAI		-0.056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs762853375; hg19: chr3-4345082;