Variant 3-86968650-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016206.4(VGLL3):c.877G>A(p.Ala293Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

VGLL3
NM_016206.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VGLL3	NM_016206.4 linkuse as main transcript	c.877G>A	p.Ala293Thr	missense_variant	3/4	ENST00000398399.7
VGLL3	NM_001320493.2 linkuse as main transcript	c.877G>A	p.Ala293Thr	missense_variant	3/4
VGLL3	NM_001320494.2 linkuse as main transcript	c.718G>A	p.Ala240Thr	missense_variant	3/4
VGLL3	XM_006713138.5 linkuse as main transcript	c.874G>A	p.Ala292Thr	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VGLL3	ENST00000398399.7 linkuse as main transcript	c.877G>A	p.Ala293Thr	missense_variant	3/4	1	NM_016206.4	P1	A8MV65-1
VGLL3	ENST00000383698.3 linkuse as main transcript	c.877G>A	p.Ala293Thr	missense_variant	3/4	1			A8MV65-2
VGLL3	ENST00000637106.1 linkuse as main transcript			upstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249350

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135282

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

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:

0.00000342

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000826

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

May 03, 2023

The c.877G>A (p.A293T) 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 877, causing the alanine (A) at amino acid position 293 to be replaced by a threonine (T). 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

0.093

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.072

Sift

Benign

0.29

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.61

P;.

Vest4

0.65

MutPred

0.38

Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);

MVP

0.53

MPC

0.35

ClinPred

0.56

GERP RS

5.8

Varity_R

0.077

gMVP

0.36

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