3-86968650-C-A

Variant names:

• chr3-86968650-C-A
• rs779567619
• NM_016206.4:c.877G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016206.4(VGLL3):​c.877G>T​(p.Ala293Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A293T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VGLL3 NM_016206.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30933252).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016206.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VGLL3	NM_016206.4	MANE Select	c.877G>T	p.Ala293Ser	missense	Exon 3 of 4	NP_057290.2	A8MV65-1
	VGLL3	NM_001320493.2		c.877G>T	p.Ala293Ser	missense	Exon 3 of 4	NP_001307422.1	A8MV65-2
	VGLL3	NM_001320494.2		c.718G>T	p.Ala240Ser	missense	Exon 3 of 4	NP_001307423.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VGLL3	ENST00000398399.7	TSL:1 MANE Select	c.877G>T	p.Ala293Ser	missense	Exon 3 of 4	ENSP00000381436.2	A8MV65-1
	VGLL3	ENST00000383698.3	TSL:1	c.877G>T	p.Ala293Ser	missense	Exon 3 of 4	ENSP00000373199.3	A8MV65-2
	VGLL3	ENST00000852930.1		c.874G>T	p.Ala292Ser	missense	Exon 3 of 4	ENSP00000522989.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.079
Sift	Benign	0.17	T
Sift4G	Benign	0.24	T
Polyphen		0.61	P
Vest4		0.42
MutPred		0.40		Loss of helix (P = 0.0093)
MVP		0.55
MPC		0.34
ClinPred		0.88	D
GERP RS		5.8
Varity_R		0.076
gMVP		0.26
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs779567619; hg19: chr3-87017800;