3-86969099-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_016206.4(VGLL3):c.428G>A(p.Arg143Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,604,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
VGLL3
NM_016206.4 missense
NM_016206.4 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 5.38
Genes affected
VGLL3 (HGNC:24327): (vestigial like family member 3) Predicted to enable protein C-terminus binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active 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=0.34762958).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VGLL3 | NM_016206.4 | c.428G>A | p.Arg143Gln | missense_variant | 3/4 | ENST00000398399.7 | NP_057290.2 | |
VGLL3 | NM_001320493.2 | c.428G>A | p.Arg143Gln | missense_variant | 3/4 | NP_001307422.1 | ||
VGLL3 | NM_001320494.2 | c.269G>A | p.Arg90Gln | missense_variant | 3/4 | NP_001307423.1 | ||
VGLL3 | XM_006713138.5 | c.425G>A | p.Arg142Gln | missense_variant | 3/4 | XP_006713201.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VGLL3 | ENST00000398399.7 | c.428G>A | p.Arg143Gln | missense_variant | 3/4 | 1 | NM_016206.4 | ENSP00000381436 | P1 | |
VGLL3 | ENST00000383698.3 | c.428G>A | p.Arg143Gln | missense_variant | 3/4 | 1 | ENSP00000373199 | |||
VGLL3 | ENST00000494229.1 | c.230G>A | p.Arg77Gln | missense_variant | 3/3 | 3 | ENSP00000419115 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152102Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000831 AC: 2AN: 240760Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131030
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GnomAD4 exome AF: 0.0000172 AC: 25AN: 1451970Hom.: 0 Cov.: 31 AF XY: 0.0000167 AC XY: 12AN XY: 720698
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74300
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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 | Mar 25, 2024 | The c.428G>A (p.R143Q) alteration is located in exon 3 (coding exon 3) of the VGLL3 gene. This alteration results from a G to A substitution at nucleotide position 428, causing the arginine (R) at amino acid position 143 to be replaced by a glutamine (Q). 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
Benign
CADD
Benign
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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