3-11558592-C-G

Position:

• chr3-11558592-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001128219.3(VGLL4):​c.855G>C​(p.Met285Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: VGLL4 NM_001128219.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89

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]

ATG7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26640898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VGLL4	NM_001128219.3	c.855G>C	p.Met285Ile	missense_variant	5/5	ENST00000430365.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VGLL4	ENST00000430365.7	c.855G>C	p.Met285Ile	missense_variant	5/5	2	NM_001128219.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.855G>C (p.M285I) alteration is located in exon 5 (coding exon 5) of the VGLL4 gene. This alteration results from a G to C substitution at nucleotide position 855, causing the methionine (M) at amino acid position 285 to be replaced by an isoleucine (I). 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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;T;.;.;.;T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T;D;T;D;D;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.27	T;T;T;T;T;T
MetaSVM	Benign	-0.51	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.92	N;N;N;N;N;.
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D;D;D;D;.
Sift4G	Benign	0.25	T;T;T;.;T;T
Polyphen		0.98	.;.;D;D;D;.
Vest4		0.45
MutPred		0.25		.;.;.;.;Gain of sheet (P = 0.0344);.;
MVP		0.21
MPC		0.21
ClinPred		0.95	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-11600066;