rs1344083

Variant names:

• chr3-86966777-A-G
• rs1344083
• NM_016206.4:c.937+1813T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016206.4(VGLL3):​c.937+1813T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.011 (0 hom., cov: 0)
• Consequence: VGLL3 NM_016206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VGLL3	NM_016206.4	c.937+1813T>C		intron_variant	Intron 3 of 3	ENST00000398399.7	NP_057290.2
VGLL3	NM_001320493.2	c.937+1813T>C		intron_variant	Intron 3 of 3		NP_001307422.1
VGLL3	NM_001320494.2	c.778+1813T>C		intron_variant	Intron 3 of 3		NP_001307423.1
VGLL3	XM_006713138.5	c.934+1813T>C		intron_variant	Intron 3 of 3		XP_006713201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VGLL3	ENST00000398399.7	c.937+1813T>C		intron_variant	Intron 3 of 3	1	NM_016206.4	ENSP00000381436.2
VGLL3	ENST00000383698.3	c.937+1813T>C		intron_variant	Intron 3 of 3	1		ENSP00000373199.3
VGLL3	ENST00000637106.1	n.40+1813T>C		intron_variant	Intron 1 of 5	5		ENSP00000489678.1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 139 AN: 12896 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00400

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00314

Gnomad FIN AF: 0.00136

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00489

Gnomad OTH AF: 0.00595

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0108 AC: 139 AN: 12892 Hom.: 0 Cov.: 0 AF XY: 0.0109 AC XY: 67 AN XY: 6124

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0334 AC: 99 AN: 2962

American (AMR) AF: 0.00399 AC: 6 AN: 1502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 416

East Asian (EAS) AF: 0.00 AC: 0 AN: 374

South Asian (SAS) AF: 0.00325 AC: 1 AN: 308

European-Finnish (FIN) AF: 0.00136 AC: 1 AN: 738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 28

European-Non Finnish (NFE) AF: 0.00490 AC: 31 AN: 6332

Other (OTH) AF: 0.00575 AC: 1 AN: 174

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00253 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.39
PhyloP100		-1.1

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: rs1344083; hg19: chr3-87015927; COSMIC: COSV67354734; COSMIC: COSV67354734;