rs1349962764

Variant names:

• chr19-4258255-G-A
• rs1349962764
• NM_018074.6:c.419G>A

Variant summary

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

The NM_018074.6(YJU2):​c.419G>A​(p.Arg140Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,400,996 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: 0.0000014 (0 hom.)
• Consequence: YJU2 NM_018074.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.44
• 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.419G>A	p.Arg140Gln	missense	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.419G>A	p.Arg140Gln	missense	Exon 5 of 8	ENSP00000262962.6	Q9BW85
	YJU2	ENST00000872338.1		c.419G>A	p.Arg140Gln	missense	Exon 5 of 8	ENSP00000542397.1
	YJU2	ENST00000596496.1	TSL:3	c.314G>A	p.Arg105Gln	missense	Exon 5 of 5	ENSP00000472772.1	M0R2S3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 159174 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1400996 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 691112

African (AFR) AF: 0.00 AC: 0 AN: 31830

American (AMR) AF: 0.00 AC: 0 AN: 35738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 36094

South Asian (SAS) AF: 0.00 AC: 0 AN: 79344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1079922

Other (OTH) AF: 0.00 AC: 0 AN: 58094

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	Pathogenic	0.95
BayesDel_addAF	Benign	0.00082	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.95	T
PhyloP100		9.4
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.91	P
Vest4		0.90
MutPred		0.46		Loss of stability (P = 0.0556)
MVP		0.65
MPC		1.9
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.86
gMVP		0.50
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1349962764; hg19: chr19-4258252;