rs12634559

Variant names:

• chr3-190870555-G-A
• rs12634559
• ENST00000479491.5:n.85-11539C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000479491.5(GMNC):​n.85-11539C>T variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 5 publications found

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]

ENSG00000296664 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMNC	ENST00000479491.5	n.85-11539C>T		intron_variant	Intron 1 of 3	4
ENSG00000296664	ENST00000741067.1	n.96+1239G>A		intron_variant	Intron 1 of 3

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

African (AFR) AF: 0.798 AC: 33086 AN: 41458

American (AMR) AF: 0.438 AC: 6689 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1348 AN: 3472

East Asian (EAS) AF: 0.642 AC: 3321 AN: 5170

South Asian (SAS) AF: 0.534 AC: 2573 AN: 4814

European-Finnish (FIN) AF: 0.321 AC: 3396 AN: 10564

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20460 AN: 67920

Other (OTH) AF: 0.452 AC: 953 AN: 2110

Alfa AF: 0.361 Hom.: 19783

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
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs12634559; hg19: chr3-190588344;