chr3-86978548-C-A

Variant names:

• chr3-86978548-C-A
• rs1705255730
• NM_016206.4:c.381G>T

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.381G>T​(p.Met127Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: VGLL3 NM_016206.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• 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=0.13816002).

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.381G>T	p.Met127Ile	missense	Exon 2 of 4	NP_057290.2	A8MV65-1
	VGLL3	NM_001320493.2		c.381G>T	p.Met127Ile	missense	Exon 2 of 4	NP_001307422.1	A8MV65-2
	VGLL3	NM_001320494.2		c.222G>T	p.Met74Ile	missense	Exon 2 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.381G>T	p.Met127Ile	missense	Exon 2 of 4	ENSP00000381436.2	A8MV65-1
	VGLL3	ENST00000383698.3	TSL:1	c.381G>T	p.Met127Ile	missense	Exon 2 of 4	ENSP00000373199.3	A8MV65-2
	VGLL3	ENST00000852930.1		c.378G>T	p.Met126Ile	missense	Exon 2 of 4	ENSP00000522989.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461816 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.24
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.043
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.038
Sift	Benign	0.18	T
Sift4G	Benign	0.19	T
Polyphen		0.0050	B
Vest4		0.29
MutPred		0.32		Loss of glycosylation at S125 (P = 0.0304)
MVP		0.18
MPC		0.14
ClinPred		0.47	T
GERP RS		5.3
Varity_R		0.12
gMVP		0.13
Mutation Taster		=90/10	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: rs1705255730; hg19: chr3-87027698;