19-4249256-C-T

Variant summary

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

The NM_018074.6(YJU2):​c.53C>T​(p.Ser18Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

YJU2
NM_018074.6 missense

Scores

6
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
YJU2NM_018074.6 linkc.53C>T p.Ser18Leu missense_variant Exon 2 of 8 ENST00000262962.12 NP_060544.2 Q9BW85

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
YJU2ENST00000262962.12 linkc.53C>T p.Ser18Leu missense_variant Exon 2 of 8 1 NM_018074.6 ENSP00000262962.6 Q9BW85
YJU2ENST00000596496 linkc.-53C>T 5_prime_UTR_variant Exon 2 of 5 3 ENSP00000472772.1 M0R2S3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152100
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
251022
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135688
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000580
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000137
AC:
2
AN:
1461540
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000448
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152100
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 10, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.53C>T (p.S18L) alteration is located in exon 2 (coding exon 2) of the CCDC94 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the serine (S) at amino acid position 18 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
0.33
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.16
T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.47
T
MetaSVM
Benign
-0.65
T
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
0.96
D
Vest4
0.36
MutPred
0.41
Gain of catalytic residue at S18 (P = 0.0135);
MVP
0.71
MPC
2.0
ClinPred
0.99
D
GERP RS
6.0
Varity_R
0.66
gMVP
0.70

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748678607; hg19: chr19-4249253; API