Variant chr3-11564970-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001128219.3(VGLL4):c.322C>T(p.Arg108Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000057 in 1,542,952 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 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

VGLL4
NM_001128219.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.30

Variant links:

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]

VGLL4 links:

ATG7 (HGNC:):

ATG7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23341098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VGLL4	NM_001128219.3 linkuse as main transcript	c.322C>T	p.Arg108Cys	missense_variant	3/5	ENST00000430365.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VGLL4	ENST00000430365.7 linkuse as main transcript	c.322C>T	p.Arg108Cys	missense_variant	3/5	2	NM_001128219.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000836

AC:

AN:

191348

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

105276

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000566

Gnomad ASJ exome

AF:

0.000152

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000219

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.0000604

AC:

AN:

1390772

Hom.:

Cov.:

AF XY:

0.0000423

AC XY:

AN XY:

685360

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000590

Gnomad4 ASJ exome

AF:

0.0000432

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.0000520

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000538

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000330

AC:

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

Oct 25, 2022

The c.322C>T (p.R108C) 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 322, causing the arginine (R) at amino acid position 108 to be replaced by a cysteine (C). 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

0.19

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.096

T;T;.;.;.;T;T;.;.;T;T;.;T;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.23

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.38

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.2

N;N;D;N;N;.;D;D;D;D;.;D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

D;D;D;D;D;.;D;D;D;D;.;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;.;D;D;.;.;D;.;D;.;.;.

Polyphen

1.0

.;.;D;D;D;.;.;.;.;.;.;.;.;.

Vest4

0.76

MVP

0.42

MPC

0.89

ClinPred

0.26

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.45

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over