Variant 3-86978702-T-G 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_016206.4(VGLL3):c.227A>C(p.Asp76Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 152,082 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 0.000013 ( 0 hom., cov: 32)

Consequence

VGLL3
NM_016206.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12478697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL3	NM_016206.4 linkuse as main transcript	c.227A>C	p.Asp76Ala	missense_variant	2/4	ENST00000398399.7	NP_057290.2	A8MV65-1
VGLL3	NM_001320493.2 linkuse as main transcript	c.227A>C	p.Asp76Ala	missense_variant	2/4		NP_001307422.1	A8MV65-2
VGLL3	XM_006713138.5 linkuse as main transcript	c.224A>C	p.Asp75Ala	missense_variant	2/4		XP_006713201.1
VGLL3	NM_001320494.2 linkuse as main transcript	c.127-59A>C		intron_variant			NP_001307423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VGLL3	ENST00000398399.7 linkuse as main transcript	c.227A>C	p.Asp76Ala	missense_variant	2/4	1	NM_016206.4	ENSP00000381436.2	A8MV65-1
VGLL3	ENST00000383698.3 linkuse as main transcript	c.227A>C	p.Asp76Ala	missense_variant	2/4	1		ENSP00000373199.3	A8MV65-2
VGLL3	ENST00000494229.1 linkuse as main transcript	c.85-59A>C		intron_variant		3		ENSP00000419115.1	H7C571

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

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

Oct 24, 2023

The c.227A>C (p.D76A) alteration is located in exon 2 (coding exon 2) of the VGLL3 gene. This alteration results from a A to C substitution at nucleotide position 227, causing the aspartic acid (D) at amino acid position 76 to be replaced by an alanine (A). 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

0.29

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.085

Eigen_PC

Benign

0.085

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.094

Sift

Benign

0.045

D;D

Sift4G

Benign

0.12

T;T

Polyphen

0.19

B;.

Vest4

0.34

MutPred

0.24

Loss of glycosylation at K75 (P = 0.0362);Loss of glycosylation at K75 (P = 0.0362);

MVP

0.24

MPC

0.39

ClinPred

0.82

GERP RS

5.1

Varity_R

0.28

gMVP

0.35

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