3-86969099-C-T

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

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38
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 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
VGLL3NM_016206.4 linkuse as main transcriptc.428G>A p.Arg143Gln missense_variant 3/4 ENST00000398399.7 NP_057290.2
VGLL3NM_001320493.2 linkuse as main transcriptc.428G>A p.Arg143Gln missense_variant 3/4 NP_001307422.1
VGLL3NM_001320494.2 linkuse as main transcriptc.269G>A p.Arg90Gln missense_variant 3/4 NP_001307423.1
VGLL3XM_006713138.5 linkuse as main transcriptc.425G>A p.Arg142Gln 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.428G>A p.Arg143Gln missense_variant 3/41 NM_016206.4 ENSP00000381436 P1A8MV65-1
VGLL3ENST00000383698.3 linkuse as main transcriptc.428G>A p.Arg143Gln missense_variant 3/41 ENSP00000373199 A8MV65-2
VGLL3ENST00000494229.1 linkuse as main transcriptc.230G>A p.Arg77Gln missense_variant 3/33 ENSP00000419115

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152102
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000831
AC:
2
AN:
240760
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
131030
show subpopulations
Gnomad AFR exome
AF:
0.0000678
Gnomad AMR exome
AF:
0.0000295
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:
0.0000172
AC:
25
AN:
1451970
Hom.:
0
Cov.:
31
AF XY:
0.0000167
AC XY:
12
AN XY:
720698
show subpopulations
Gnomad4 AFR exome
AF:
0.0000902
Gnomad4 AMR exome
AF:
0.0000452
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000235
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000145
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152102
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.00000828
AC:
1

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 GeneticsMar 25, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
22
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.029
T;.
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.35
T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
1.9
M;M
MutationTaster
Benign
0.94
D;D
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.11
Sift
Benign
0.16
T;T
Sift4G
Benign
0.18
T;T
Polyphen
0.83
P;.
Vest4
0.61
MVP
0.38
MPC
0.58
ClinPred
0.36
T
GERP RS
5.9
Varity_R
0.072
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs772107874; hg19: chr3-87018249; COSMIC: COSV67354420; COSMIC: COSV67354420; API