Variant 3-86968884-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000398399.7(VGLL3):c.643G>A(p.Val215Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VGLL3
ENST00000398399.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

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]

VGLL3 links:

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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=0.40121514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VGLL3	NM_016206.4 linkuse as main transcript	c.643G>A	p.Val215Met	missense_variant	3/4	ENST00000398399.7	NP_057290.2
VGLL3	NM_001320493.2 linkuse as main transcript	c.643G>A	p.Val215Met	missense_variant	3/4		NP_001307422.1
VGLL3	NM_001320494.2 linkuse as main transcript	c.484G>A	p.Val162Met	missense_variant	3/4		NP_001307423.1
VGLL3	XM_006713138.5 linkuse as main transcript	c.640G>A	p.Val214Met	missense_variant	3/4		XP_006713201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL3	ENST00000398399.7 linkuse as main transcript	c.643G>A	p.Val215Met	missense_variant	3/4	1	NM_016206.4	ENSP00000381436	P1	A8MV65-1
VGLL3	ENST00000383698.3 linkuse as main transcript	c.643G>A	p.Val215Met	missense_variant	3/4	1		ENSP00000373199		A8MV65-2
VGLL3	ENST00000494229.1 linkuse as main transcript	c.445G>A	p.Val149Met	missense_variant	3/3	3		ENSP00000419115

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Dec 09, 2023

The c.643G>A (p.V215M) 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 643, causing the valine (V) at amino acid position 215 to be replaced by a methionine (M). 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

0.16

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.022

T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.086

Sift

Benign

0.033

D;D

Sift4G

Benign

0.38

T;T

Polyphen

0.95

P;.

Vest4

0.65

MutPred

0.20

Gain of glycosylation at Y219 (P = 4e-04);Gain of glycosylation at Y219 (P = 4e-04);

MVP

0.35

MPC

0.38

ClinPred

0.74

GERP RS

5.8

Varity_R

0.16

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over