rs779567619

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-86968650-C-A
• chr3-86968650-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VGLL3	NM_016206.4	c.877G>T	p.Ala293Ser	missense_variant	Exon 3 of 4	ENST00000398399.7	NP_057290.2
VGLL3	NM_001320493.2	c.877G>T	p.Ala293Ser	missense_variant	Exon 3 of 4		NP_001307422.1
VGLL3	NM_001320494.2	c.718G>T	p.Ala240Ser	missense_variant	Exon 3 of 4		NP_001307423.1
VGLL3	XM_006713138.5	c.874G>T	p.Ala292Ser	missense_variant	Exon 3 of 4		XP_006713201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VGLL3	ENST00000398399.7	c.877G>T	p.Ala293Ser	missense_variant	Exon 3 of 4	1	NM_016206.4	ENSP00000381436.2
VGLL3	ENST00000383698.3	c.877G>T	p.Ala293Ser	missense_variant	Exon 3 of 4	1		ENSP00000373199.3
VGLL3	ENST00000494229.1	c.*53G>T		downstream_gene_variant		3		ENSP00000419115.1
VGLL3	ENST00000637106.1	n.-21G>T		upstream_gene_variant		5		ENSP00000489678.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.079
Sift	Benign	0.17	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.61	P;.
Vest4		0.42
MutPred		0.40		Loss of helix (P = 0.0093);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

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

Other links and lift over

dbSNP: rs779567619; hg19: chr3-87017800;