rs17023661

Positions:

• chr3-86919359-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_001740802.2(LOC105377196):​n.793-3016G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 152,150 control chromosomes in the GnomAD database, including 1,106 homozygotes. 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 0.082 (1106 hom., cov: 32)
• Consequence: LOC105377196 XR_001740802.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

Genes affected

LOC105377196 (HGNC:):

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105377196	XR_001740802.2	n.793-3016G>A		intron_variant, non_coding_transcript_variant
LOC105377196	XR_001740803.2	n.792+5072G>A		intron_variant, non_coding_transcript_variant
LOC105377196	XR_002959628.1	n.793-3016G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL3	ENST00000637106.1	c.*15-10301G>A		intron_variant, NMD_transcript_variant		5		ENSP00000489678

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12504 AN: 152032 Hom.: 1099 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0386

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00651

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0824 AC: 12530 AN: 152150 Hom.: 1106 Cov.: 32 AF XY: 0.0853 AC XY: 6344 AN XY: 74390

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.0376

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.00651

Gnomad4 OTH AF: 0.0771

Alfa AF: 0.0279 Hom.: 482

Bravo AF: 0.100

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17023661; hg19: chr3-86968509;