chr19-4262065-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_018074.6(YJU2):​c.659C>T​(p.Ser220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

YJU2
NM_018074.6 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.119
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity YJU2_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07492387).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
YJU2NM_018074.6 linkc.659C>T p.Ser220Leu missense_variant Exon 6 of 8 ENST00000262962.12 NP_060544.2 Q9BW85

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
YJU2ENST00000262962.12 linkc.659C>T p.Ser220Leu missense_variant Exon 6 of 8 1 NM_018074.6 ENSP00000262962.6 Q9BW85

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1460242
Hom.:
0
Cov.:
31
AF XY:
0.00000551
AC XY:
4
AN XY:
726476
show subpopulations
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:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 24, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.659C>T (p.S220L) 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 659, causing the serine (S) at amino acid position 220 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
0.064
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
7.1
DANN
Benign
0.83
DEOGEN2
Benign
0.028
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.075
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.62
N
REVEL
Benign
0.0060
Sift
Benign
0.11
T
Sift4G
Benign
0.29
T
Polyphen
0.14
B
Vest4
0.11
MVP
0.15
MPC
0.077
ClinPred
0.040
T
GERP RS
-0.14
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.049
gMVP
0.11

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: rs151025034; hg19: chr19-4262062; API