chr3-86968640-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_016206.4(VGLL3):​c.887G>T​(p.Gly296Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

VGLL3
NM_016206.4 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.34
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VGLL3NM_016206.4 linkuse as main transcriptc.887G>T p.Gly296Val missense_variant 3/4 ENST00000398399.7 NP_057290.2
VGLL3NM_001320493.2 linkuse as main transcriptc.887G>T p.Gly296Val missense_variant 3/4 NP_001307422.1
VGLL3NM_001320494.2 linkuse as main transcriptc.728G>T p.Gly243Val missense_variant 3/4 NP_001307423.1
VGLL3XM_006713138.5 linkuse as main transcriptc.884G>T p.Gly295Val missense_variant 3/4 XP_006713201.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VGLL3ENST00000398399.7 linkuse as main transcriptc.887G>T p.Gly296Val missense_variant 3/41 NM_016206.4 ENSP00000381436 P1A8MV65-1
VGLL3ENST00000383698.3 linkuse as main transcriptc.887G>T p.Gly296Val missense_variant 3/41 ENSP00000373199 A8MV65-2
VGLL3ENST00000637106.1 linkuse as main transcript upstream_gene_variant 5 ENSP00000489678

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsDec 18, 2023The c.887G>T (p.G296V) alteration is located in exon 3 (coding exon 3) of the VGLL3 gene. This alteration results from a G to T substitution at nucleotide position 887, causing the glycine (G) at amino acid position 296 to be replaced by a valine (V). 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
Uncertain
0.56
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;.
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.053
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Benign
-0.33
T
MutationAssessor
Uncertain
2.7
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-4.3
D;D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.013
D;D
Polyphen
0.99
D;.
Vest4
0.92
MutPred
0.57
Loss of glycosylation at T291 (P = 0.029);Loss of glycosylation at T291 (P = 0.029);
MVP
0.80
MPC
0.64
ClinPred
0.98
D
GERP RS
5.8
Varity_R
0.58
gMVP
0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-87017790; API