3-86990639-C-T

Position:

• chr3-86990639-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The ENST00000398399.7(VGLL3):​c.105G>A​(p.Pro35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000328 in 1,218,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: VGLL3 ENST00000398399.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.364

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 3-86990639-C-T is Benign according to our data. Variant chr3-86990639-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653986.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.364 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL3	NM_016206.4	c.105G>A	p.Pro35=	synonymous_variant	1/4	ENST00000398399.7	NP_057290.2
VGLL3	NM_001320493.2	c.105G>A	p.Pro35=	synonymous_variant	1/4		NP_001307422.1
VGLL3	NM_001320494.2	c.105G>A	p.Pro35=	synonymous_variant	1/4		NP_001307423.1
VGLL3	XM_006713138.5	c.105G>A	p.Pro35=	synonymous_variant	1/4		XP_006713201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL3	ENST00000398399.7	c.105G>A	p.Pro35=	synonymous_variant	1/4	1	NM_016206.4	ENSP00000381436	P1
VGLL3	ENST00000383698.3	c.105G>A	p.Pro35=	synonymous_variant	1/4	1		ENSP00000373199
VGLL3	ENST00000494229.1	c.66G>A	p.Pro22=	synonymous_variant	1/3	3		ENSP00000419115

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000328 AC: 4 AN: 1218794 Hom.: 0 Cov.: 31 AF XY: 0.00000169 AC XY: 1 AN XY: 592110

Gnomad4 AFR exome AF: 0.0000792

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000203

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

VGLL3: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	15
DANN	Benign	0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-87039789;