19-4258410-G-T

Variant names:

• chr19-4258410-G-T
• rs1373968374
• NM_018074.6:c.574G>T

Variant summary

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

The NM_018074.6(YJU2):​c.574G>T​(p.Glu192*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000695 in 1,438,020 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: YJU2 NM_018074.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25
• 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: 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_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.574G>T	p.Glu192*	stop_gained	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.574G>T	p.Glu192*	stop_gained	Exon 5 of 8	ENSP00000262962.6	Q9BW85
	YJU2	ENST00000872338.1		c.574G>T	p.Glu192*	stop_gained	Exon 5 of 8	ENSP00000542397.1
	YJU2	ENST00000596496.1	TSL:3	c.469G>T	p.Glu157*	stop_gained	Exon 5 of 5	ENSP00000472772.1	M0R2S3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000479 AC: 1 AN: 208724 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438020 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 712848

African (AFR) AF: 0.00 AC: 0 AN: 33312

American (AMR) AF: 0.00 AC: 0 AN: 40372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25552

East Asian (EAS) AF: 0.00 AC: 0 AN: 38928

South Asian (SAS) AF: 0.00 AC: 0 AN: 82344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4566

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102646

Other (OTH) AF: 0.00 AC: 0 AN: 59542

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		6.2
Vest4		0.14
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=5/195	disease causing (fs/PTC)

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: rs1373968374; hg19: chr19-4258407;