19-4258319-C-T

Variant names:

• chr19-4258319-C-T
• rs1470614975
• NM_018074.6:c.483C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018074.6(YJU2):​c.483C>T​(p.Asn161Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000421 in 1,425,636 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: 0.0000042 (0 hom.)
• Consequence: YJU2 NM_018074.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49
• Publications: 0 publications found

Genes affected

YJU2 (HGNC:25518): (YJU2 splicing factor homolog) Predicted to enable metal ion binding activity. Predicted to be involved in RNA splicing and negative regulation of DNA damage response, signal transduction by p53 class mediator. Part of U2-type catalytic step 1 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=2.49 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018074.6. 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
	YJU2	NM_018074.6	MANE Select	c.483C>T	p.Asn161Asn	synonymous	Exon 5 of 8	NP_060544.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YJU2	ENST00000262962.12	TSL:1 MANE Select	c.483C>T	p.Asn161Asn	synonymous	Exon 5 of 8	ENSP00000262962.6	Q9BW85
	YJU2	ENST00000872338.1		c.483C>T	p.Asn161Asn	synonymous	Exon 5 of 8	ENSP00000542397.1
	YJU2	ENST00000596496.1	TSL:3	c.378C>T	p.Asn126Asn	synonymous	Exon 5 of 5	ENSP00000472772.1	M0R2S3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000421 AC: 6 AN: 1425636 Hom.: 0 Cov.: 32 AF XY: 0.00000284 AC XY: 2 AN XY: 705214

African (AFR) AF: 0.00 AC: 0 AN: 33146

American (AMR) AF: 0.00 AC: 0 AN: 37858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25318

East Asian (EAS) AF: 0.00 AC: 0 AN: 38520

South Asian (SAS) AF: 0.00 AC: 0 AN: 81068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00000548 AC: 6 AN: 1094330

Other (OTH) AF: 0.00 AC: 0 AN: 59136

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		2.5

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: rs1470614975; hg19: chr19-4258316;