3-11564994-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001128219.3(VGLL4):c.298C>T(p.Arg100Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000396 in 1,513,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
VGLL4
NM_001128219.3 missense
NM_001128219.3 missense
Scores
3
9
6
Clinical Significance
Conservation
PhyloP100: 3.48
Genes affected
VGLL4 (HGNC:28966): (vestigial like family member 4) Predicted to enable transcription coactivator binding activity. Involved in negative regulation of Wnt signaling pathway; negative regulation of cell growth; and negative regulation of hippo signaling. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2659011).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VGLL4 | NM_001128219.3 | c.298C>T | p.Arg100Cys | missense_variant | 3/5 | ENST00000430365.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VGLL4 | ENST00000430365.7 | c.298C>T | p.Arg100Cys | missense_variant | 3/5 | 2 | NM_001128219.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000541 AC: 9AN: 166224Hom.: 0 AF XY: 0.0000440 AC XY: 4AN XY: 90982
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GnomAD4 exome AF: 0.0000331 AC: 45AN: 1361068Hom.: 0 Cov.: 31 AF XY: 0.0000209 AC XY: 14AN XY: 668510
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GnomAD4 genome AF: 0.0000985 AC: 15AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74470
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2022 | The c.298C>T (p.R100C) alteration is located in exon 3 (coding exon 3) of the VGLL4 gene. This alteration results from a C to T substitution at nucleotide position 298, causing the arginine (R) at amino acid position 100 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;.;.;.;T;T;.;.;T;T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;D;D;D;.;D;D;D;D;.;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;.;D;D;D;D;.;D;D;D
Sift4G
Pathogenic
D;D;D;.;D;D;.;.;D;.;D;.;.;.
Polyphen
1.0
.;.;D;D;D;.;.;.;.;.;.;.;.;.
Vest4
MVP
MPC
0.83
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at