Variant 3-86990641-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016206.4(VGLL3):c.103C>A(p.Pro35Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,376,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

VGLL3
NM_016206.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06316337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL3	NM_016206.4 link	c.103C>A	p.Pro35Thr	missense_variant	1/4	ENST00000398399.7	NP_057290.2	A8MV65-1
VGLL3	NM_001320493.2 link	c.103C>A	p.Pro35Thr	missense_variant	1/4		NP_001307422.1	A8MV65-2
VGLL3	NM_001320494.2 link	c.103C>A	p.Pro35Thr	missense_variant	1/4		NP_001307423.1
VGLL3	XM_006713138.5 link	c.103C>A	p.Pro35Thr	missense_variant	1/4		XP_006713201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VGLL3	ENST00000398399.7 link	c.103C>A	p.Pro35Thr	missense_variant	1/4	1	NM_016206.4	ENSP00000381436.2	A8MV65-1
VGLL3	ENST00000383698.3 link	c.103C>A	p.Pro35Thr	missense_variant	1/4	1		ENSP00000373199.3	A8MV65-2
VGLL3	ENST00000494229.1 link	c.61C>A	p.Pro21Thr	missense_variant	1/3	3		ENSP00000419115.1	H7C571

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

GnomAD4 exome

AF:

8.17e-7

AC:

AN:

1224662

Hom.:

Cov.:

AF XY:

0.00000168

AC XY:

AN XY:

595608

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:

0.0000204

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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:

0.00

Bravo

AF:

0.00000756

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

Nov 29, 2021

The c.103C>A (p.P35T) alteration is located in exon 1 (coding exon 1) of the VGLL3 gene. This alteration results from a C to A substitution at nucleotide position 103, causing the proline (P) at amino acid position 35 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

0.062

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.079

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.94

N;N

REVEL

Benign

0.041

Sift

Benign

0.22

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0

B;.

Vest4

0.17

MutPred

0.23

Gain of glycosylation at Y32 (P = 0.005);Gain of glycosylation at Y32 (P = 0.005);

MVP

0.076

MPC

0.14

ClinPred

0.13

GERP RS

1.6

Varity_R

0.083

gMVP

0.30

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