chr3-11559362-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001128219.3(VGLL4):c.589G>A(p.Gly197Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000832 in 1,550,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

VGLL4
NM_001128219.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.135

Publications

0 publications found

Variant links:

Genes affected

VGLL4 (HGNC:28966): (vestigial like family member 4) Predicted to enable transcription coactivator binding activity. Involved in negative regulation of Wnt signaling pathway; negative regulation of cell growth; and negative regulation of hippo signaling. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

VGLL4 links:

ATG7 (HGNC:16935): (autophagy related 7) This gene encodes an E1-like activating enzyme that is essential for autophagy and cytoplasmic to vacuole transport. The encoded protein is also thought to modulate p53-dependent cell cycle pathways during prolonged metabolic stress. It has been associated with multiple functions, including axon membrane trafficking, axonal homeostasis, mitophagy, adipose differentiation, and hematopoietic stem cell maintenance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ATG7 Gene-Disease associations (from GenCC):

spinocerebellar ataxia, autosomal recessive 31
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ATG7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07172337).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VGLL4	NM_001128219.3	MANE Select	c.589G>A	p.Gly197Arg	missense	Exon 4 of 5	NP_001121691.1	Q14135-4
VGLL4	NM_001284390.2		c.586G>A	p.Gly196Arg	missense	Exon 6 of 7	NP_001271319.1	A0A0A6YYI5
VGLL4	NM_014667.4		c.571G>A	p.Gly191Arg	missense	Exon 5 of 6	NP_055482.2	Q14135-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VGLL4	ENST00000430365.7	TSL:2 MANE Select	c.589G>A	p.Gly197Arg	missense	Exon 4 of 5	ENSP00000404251.2	Q14135-4
VGLL4	ENST00000426568.5	TSL:1	c.586G>A	p.Gly196Arg	missense	Exon 6 of 7	ENSP00000413030.2	A0A0A6YYI5
VGLL4	ENST00000273038.7	TSL:1	c.571G>A	p.Gly191Arg	missense	Exon 5 of 6	ENSP00000273038.3	Q14135-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000257

AC:

AN:

155354

AF XY:

0.0000242

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000664

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000808

AC:

113

AN:

1398462

Hom.:

Cov.:

AF XY:

0.0000725

AC XY:

AN XY:

689806

show subpopulations

African (AFR)

AF:

0.0000945

AC:

AN:

31746

American (AMR)

AF:

0.00

AC:

AN:

35730

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25008

East Asian (EAS)

AF:

0.0000278

AC:

AN:

35982

South Asian (SAS)

AF:

0.00

AC:

AN:

79176

European-Finnish (FIN)

AF:

0.0000205

AC:

AN:

48866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4902

European-Non Finnish (NFE)

AF:

0.0000964

AC:

104

AN:

1079188

Other (OTH)

AF:

0.0000691

AC:

AN:

57864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68048

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000851

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000271

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.026

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.030

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.1

PhyloP100

-0.14

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

REVEL

Benign

0.10

Sift

Benign

0.47

Sift4G

Benign

0.64

Polyphen

0.85

Vest4

0.37

MutPred

0.15

Gain of solvent accessibility (P = 0.0037)

MVP

0.12

MPC

0.51

ClinPred

0.12

GERP RS

2.5

gMVP

0.16

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over