Variant chrX-136548751-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016267.4(VGLL1):c.377G>A(p.Arg126Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000463 in 1,210,430 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 201 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., 23 hem., cov: 23)

Exomes 𝑓: 0.00044 ( 0 hom. 178 hem. )

Consequence

VGLL1
NM_016267.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.387

Variant links:

Genes affected

VGLL1 (HGNC:20985): (vestigial like family member 1) The protein encoded by this gene binds proteins of the TEA domain family of transcription factors (TEFs) through the Vg (vestigial) homology region found in its N-terminus. It may thus function as a specific coactivator for the mammalian TEFs. [provided by RefSeq, Sep 2009]

VGLL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009312481).

BP6

Variant X-136548751-G-A is Benign according to our data. Variant chrX-136548751-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2229452.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VGLL1	NM_016267.4 linkuse as main transcript	c.377G>A	p.Arg126Gln	missense_variant	3/5	ENST00000370634.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
VGLL1	ENST00000370634.8 linkuse as main transcript	c.377G>A	p.Arg126Gln	missense_variant	3/5	1	NM_016267.4	P1
VGLL1	ENST00000440515.5 linkuse as main transcript	c.272G>A	p.Arg91Gln	missense_variant	2/4	3
VGLL1	ENST00000456412.1 linkuse as main transcript	c.41-2017G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000740

AC:

AN:

112115

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

34289

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000939

Gnomad ASJ

AF:

0.00340

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000488

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000545

AC:

100

AN:

183435

Hom.:

AF XY:

0.000633

AC XY:

AN XY:

67885

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00307

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000625

Gnomad NFE exome

AF:

0.000782

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000435

AC:

478

AN:

1098262

Hom.:

Cov.:

AF XY:

0.000490

AC XY:

178

AN XY:

363616

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00346

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.000765

Gnomad4 NFE exome

AF:

0.000417

Gnomad4 OTH exome

AF:

0.000564

GnomAD4 genome

AF:

0.000740

AC:

AN:

112168

Hom.:

Cov.:

AF XY:

0.000670

AC XY:

AN XY:

34352

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.0000938

Gnomad4 ASJ

AF:

0.00340

Gnomad4 EAS

AF:

0.000283

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000488

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000582

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.000642

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.000771

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

Oct 26, 2021

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

0.070

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.35

DANN

Benign

0.53

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.53

M_CAP

Benign

0.0041

MetaRNN

Benign

0.0093

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.18

PROVEAN

Benign

0.90

REVEL

Benign

0.027

Sift

Benign

0.72

Sift4G

Benign

0.71

Polyphen

0.0020

Vest4

0.049

MVP

0.048

MPC

0.46

ClinPred

0.021

GERP RS

0.48

Varity_R

0.024

gMVP

0.058

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