19-4262095-C-T

Variant names:

• chr19-4262095-C-T
• rs1442624390
• NM_018074.6:c.689C>T

Variant summary

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

The NM_018074.6(YJU2):​c.689C>T​(p.Pro230Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000686 in 1,458,444 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: 0.0000069 (0 hom.)
• Consequence: YJU2 NM_018074.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YJU2	NM_018074.6	c.689C>T	p.Pro230Leu	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.689C>T	p.Pro230Leu	missense_variant	Exon 6 of 8	1	NM_018074.6	ENSP00000262962.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000686 AC: 10 AN: 1458444 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 725670

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: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 31, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.689C>T (p.P230L) alteration is located in exon 6 (coding exon 6) of the CCDC94 gene. This alteration results from a C to T substitution at nucleotide position 689, causing the proline (P) at amino acid position 230 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.94	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.24	T
Polyphen		0.89	P
Vest4		0.41
MutPred		0.68		Loss of glycosylation at T231 (P = 0.0613);
MVP		0.66
MPC		0.44
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.24
gMVP		0.51

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: rs1442624390; hg19: chr19-4262092;