rs199674678

Variant names:

• chr19-4262085-C-G
• rs199674678
• NM_018074.6:c.679C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-4262085-C-G
• chr19-4262085-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018074.6(YJU2):​c.679C>G​(p.Arg227Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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. R227Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: YJU2 NM_018074.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089889854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YJU2	NM_018074.6	c.679C>G	p.Arg227Gly	missense_variant	Exon 6 of 8	ENST00000262962.12	NP_060544.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YJU2	ENST00000262962.12	c.679C>G	p.Arg227Gly	missense_variant	Exon 6 of 8	1	NM_018074.6	ENSP00000262962.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.7
DANN	Benign	0.93
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.017
Sift	Benign	0.16	T
Sift4G	Benign	0.28	T
Polyphen		0.0040	B
Vest4		0.20
MutPred		0.51		Loss of methylation at R227 (P = 0.033);
MVP		0.28
MPC		0.22
ClinPred		0.089	T
GERP RS		0.85
Varity_R		0.11
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs199674678; hg19: chr19-4262082;