rs1279563337

Variant names:

• chr19-4258345-A-G
• NM_018074.6:c.509A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-4258345-A-G
• chr19-4258345-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018074.6(YJU2):​c.509A>G​(p.Glu170Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,439,128 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E170V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: YJU2 NM_018074.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.73

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YJU2	NM_018074.6	c.509A>G	p.Glu170Gly	missense_variant	Exon 5 of 8	ENST00000262962.12	NP_060544.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YJU2	ENST00000262962.12	c.509A>G	p.Glu170Gly	missense_variant	Exon 5 of 8	1	NM_018074.6	ENSP00000262962.6
YJU2	ENST00000596496.1	c.404A>G	p.Glu135Gly	missense_variant	Exon 5 of 5	3		ENSP00000472772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1439128 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713372

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000363

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.75	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.4	D;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.013	D;.
Sift4G	Uncertain	0.055	T;D
Polyphen		0.95	P;.
Vest4		0.88
MutPred		0.62		Gain of MoRF binding (P = 0.0564);.;
MVP		0.70
MPC		0.45
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.85
gMVP		0.23

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4258342;