NM_016206.4:c.670G>A

Variant names:

• chr3-86968857-C-T
• NM_016206.4:c.670G>A

Variant summary

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

The NM_016206.4(VGLL3):​c.670G>A​(p.Asp224Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.37
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.670G>A	p.Asp224Asn	missense	Exon 3 of 4	NP_057290.2	A8MV65-1
	VGLL3	NM_001320493.2		c.670G>A	p.Asp224Asn	missense	Exon 3 of 4	NP_001307422.1	A8MV65-2
	VGLL3	NM_001320494.2		c.511G>A	p.Asp171Asn	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.670G>A	p.Asp224Asn	missense	Exon 3 of 4	ENSP00000381436.2	A8MV65-1
	VGLL3	ENST00000383698.3	TSL:1	c.670G>A	p.Asp224Asn	missense	Exon 3 of 4	ENSP00000373199.3	A8MV65-2
	VGLL3	ENST00000852930.1		c.667G>A	p.Asp223Asn	missense	Exon 3 of 4	ENSP00000522989.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.31	T
Polyphen		0.79	P
Vest4		0.63
MutPred		0.28		Gain of glycosylation at Y219 (P = 4e-04)
MVP		0.46
MPC		0.23
ClinPred		0.63	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.42
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr3-87018007;