3-86990639-C-T

Variant names:

• chr3-86990639-C-T
• NM_016206.4:c.105G>A

Variant summary

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

The NM_016206.4(VGLL3):​c.105G>A​(p.Pro35Pro) 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 NM_016206.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.364
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.032).
• 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 VariationId 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 rank	MANE	Protein	UniProt
VGLL3	NM_016206.4	c.105G>A	p.Pro35Pro	synonymous_variant	Exon 1 of 4	ENST00000398399.7	NP_057290.2
VGLL3	NM_001320493.2	c.105G>A	p.Pro35Pro	synonymous_variant	Exon 1 of 4		NP_001307422.1
VGLL3	NM_001320494.2	c.105G>A	p.Pro35Pro	synonymous_variant	Exon 1 of 4		NP_001307423.1
VGLL3	XM_006713138.5	c.105G>A	p.Pro35Pro	synonymous_variant	Exon 1 of 4		XP_006713201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VGLL3	ENST00000398399.7	c.105G>A	p.Pro35Pro	synonymous_variant	Exon 1 of 4	1	NM_016206.4	ENSP00000381436.2
VGLL3	ENST00000383698.3	c.105G>A	p.Pro35Pro	synonymous_variant	Exon 1 of 4	1		ENSP00000373199.3
VGLL3	ENST00000494229.1	c.63G>A	p.Pro21Pro	synonymous_variant	Exon 1 of 3	3		ENSP00000419115.1

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

African (AFR) AF: 0.0000792 AC: 2 AN: 25240

American (AMR) AF: 0.00 AC: 0 AN: 18102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17556

East Asian (EAS) AF: 0.00 AC: 0 AN: 30832

South Asian (SAS) AF: 0.00 AC: 0 AN: 41712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4740

European-Non Finnish (NFE) AF: 0.00000203 AC: 2 AN: 986246

Other (OTH) AF: 0.00 AC: 0 AN: 48676

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.36
PromoterAI		-0.043	Neutral
Mutation Taster		=99/1	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: chr3-87039789;