3-86968640-C-A

Position:

• chr3-86968640-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016206.4(VGLL3):​c.887G>T​(p.Gly296Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VGLL3 NM_016206.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.34

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VGLL3	NM_016206.4	c.887G>T	p.Gly296Val	missense_variant	3/4	ENST00000398399.7
VGLL3	NM_001320493.2	c.887G>T	p.Gly296Val	missense_variant	3/4
VGLL3	NM_001320494.2	c.728G>T	p.Gly243Val	missense_variant	3/4
VGLL3	XM_006713138.5	c.884G>T	p.Gly295Val	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VGLL3	ENST00000398399.7	c.887G>T	p.Gly296Val	missense_variant	3/4	1	NM_016206.4	P1
VGLL3	ENST00000383698.3	c.887G>T	p.Gly296Val	missense_variant	3/4	1
VGLL3	ENST00000637106.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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.887G>T (p.G296V) alteration is located in exon 3 (coding exon 3) of the VGLL3 gene. This alteration results from a G to T substitution at nucleotide position 887, causing the glycine (G) at amino acid position 296 to be replaced by a valine (V). 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	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.99	D;.
Vest4		0.92
MutPred		0.57		Loss of glycosylation at T291 (P = 0.029);Loss of glycosylation at T291 (P = 0.029);
MVP		0.80
MPC		0.64
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.58
gMVP		0.50

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: chr3-87017790;