Variant 3-11564910-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001128219.3(VGLL4):c.382A>G(p.Thr128Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,600,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

VGLL4
NM_001128219.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.854

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013721883).

BP6

Variant 3-11564910-T-C is Benign according to our data. Variant chr3-11564910-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3188518.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL4	NM_001128219.3 linkuse as main transcript	c.382A>G	p.Thr128Ala	missense_variant	3/5	ENST00000430365.7	NP_001121691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL4	ENST00000430365.7 linkuse as main transcript	c.382A>G	p.Thr128Ala	missense_variant	3/5	2	NM_001128219.3	ENSP00000404251	P1

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151418

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000972

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000789

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:

0.00

Gnomad OTH

AF:

0.000961

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1448642

Hom.:

Cov.:

AF XY:

0.00000556

AC XY:

AN XY:

720002

show subpopulations

Gnomad4 AFR exome

AF:

0.0000913

Gnomad4 AMR exome

AF:

0.0000928

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000119

AC:

AN:

151418

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

73892

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.000789

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000961

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000208

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.059

DANN

Benign

0.60

DEOGEN2

Benign

0.0027

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

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.77

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

M_CAP

Benign

0.0040

MetaRNN

Benign

0.014

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

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.31

N;N;N;N;N;.;N;N;N;N;.;N;N

REVEL

Benign

0.067

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0010, 0.0

.;.;B;B;B;.;.;.;.;.;.;.;.

Vest4

0.076

MutPred

0.20

.;.;.;.;Loss of helix (P = 0.0196);.;.;.;.;.;.;.;.;

MVP

0.048

MPC

0.19

ClinPred

0.026

GERP RS

-4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.18

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