NM_016206.4:c.757T>A

Variant names:

• chr3-86968770-A-T
• NM_016206.4:c.757T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016206.4(VGLL3):​c.757T>A​(p.Ser253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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: 1.56
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21225819).

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.757T>A	p.Ser253Thr	missense	Exon 3 of 4	NP_057290.2	A8MV65-1
	VGLL3	NM_001320493.2		c.757T>A	p.Ser253Thr	missense	Exon 3 of 4	NP_001307422.1	A8MV65-2
	VGLL3	NM_001320494.2		c.598T>A	p.Ser200Thr	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.757T>A	p.Ser253Thr	missense	Exon 3 of 4	ENSP00000381436.2	A8MV65-1
	VGLL3	ENST00000383698.3	TSL:1	c.757T>A	p.Ser253Thr	missense	Exon 3 of 4	ENSP00000373199.3	A8MV65-2
	VGLL3	ENST00000852930.1		c.754T>A	p.Ser252Thr	missense	Exon 3 of 4	ENSP00000522989.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0063	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.21
Sift	Benign	0.40	T
Sift4G	Benign	0.60	T
Polyphen		0.99	D
Vest4		0.26
MutPred		0.30		Loss of glycosylation at S253 (P = 0.029)
MVP		0.43
MPC		0.11
ClinPred		0.44	T
GERP RS		5.9
Varity_R		0.086
gMVP		0.25
Mutation Taster		=81/19	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

hg19: chr3-87017920;