rs2754775

Positions:

• chr6-24774953-G-T

Variant summary

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

The NM_015895.5(GMNN):​c.-317G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,322 control chromosomes in the GnomAD database, including 2,010 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 0.15 (2010 hom., cov: 33)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: GMNN NM_015895.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497

Genes affected

GMNN (HGNC:17493): (geminin DNA replication inhibitor) This gene encodes a protein that plays a critical role in cell cycle regulation. The encoded protein inhibits DNA replication by binding to DNA replication factor Cdt1, preventing the incorporation of minichromosome maintenance proteins into the pre-replication complex. The encoded protein is expressed during the S and G2 phases of the cell cycle and is degraded by the anaphase-promoting complex during the metaphase-anaphase transition. Increased expression of this gene may play a role in several malignancies including colon, rectal and breast cancer. Alternatively spliced transcript variants have been observed for this gene, and two pseudogenes of this gene are located on the short arm of chromosome 16. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMNN	NM_015895.5	c.-317G>T		5_prime_UTR_variant	1/7	ENST00000230056.8
GMNN	NM_001251989.2	c.-185G>T		5_prime_UTR_variant	1/7
GMNN	NM_001251990.2	c.-109G>T		5_prime_UTR_variant	1/7
GMNN	XM_005249159.3	c.-897G>T		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMNN	ENST00000230056.8	c.-317G>T		5_prime_UTR_variant	1/7	1	NM_015895.5	P1
GMNN	ENST00000356509.7	c.-185G>T		5_prime_UTR_variant	1/7	2		P1
GMNN	ENST00000468943.1	n.5G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23269 AN: 152146 Hom.: 2008 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.121 AC: 7 AN: 58 Hom.: 0 Cov.: 0 AF XY: 0.140 AC XY: 7 AN XY: 50

Gnomad4 AFR exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.153 AC: 23294 AN: 152264 Hom.: 2010 Cov.: 33 AF XY: 0.153 AC XY: 11361 AN XY: 74466

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.0828

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.184

Alfa AF: 0.125 Hom.: 531

Bravo AF: 0.159

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.1
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2754775; hg19: chr6-24775181;