rs12634559

Positions:

• chr3-190870555-G-A

Variant summary

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

The ENST00000479491.5(GMNC):​n.85-11539C>T 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 0.475 in 151,988 control chromosomes in the GnomAD database, including 20,712 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 0.47 (20712 hom., cov: 32)
• Consequence: GMNC ENST00000479491.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

Genes affected

GMNC (HGNC:40049): (geminin coiled-coil domain containing) Predicted to enable chromatin binding activity. Predicted to be involved in DNA replication; negative regulation of DNA replication; and negative regulation of cell cycle. Predicted to act upstream of or within cilium assembly. 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMNC	ENST00000479491.5	n.85-11539C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72071 AN: 151870 Hom.: 20660 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.475 AC: 72179 AN: 151988 Hom.: 20712 Cov.: 32 AF XY: 0.479 AC XY: 35588 AN XY: 74308

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.452

Alfa AF: 0.347 Hom.: 14146

Bravo AF: 0.500

Asia WGS AF: 0.555 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12634559; hg19: chr3-190588344;