6-24780797-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015895.5(GMNN):c.129+57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 811,742 control chromosomes in the GnomAD database, including 9,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2056 hom., cov: 33)
  • Exomes 𝑓: 0.13 (7103 hom.)
• Consequence: GMNN NM_015895.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0600

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-24780797-A-G is Benign according to our data. Variant chr6-24780797-A-G is described in ClinVar as [Benign]. Clinvar id is 1266816.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.129+57A>G		intron_variant		ENST00000230056.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMNN	ENST00000230056.8	c.129+57A>G		intron_variant		1	NM_015895.5	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23776 AN: 152098 Hom.: 2054 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.0999

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.134 AC: 88634 AN: 659524 Hom.: 7103 AF XY: 0.140 AC XY: 49120 AN XY: 350876

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.0957

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.0971

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.156 AC: 23800 AN: 152218 Hom.: 2056 Cov.: 33 AF XY: 0.156 AC XY: 11638 AN XY: 74418

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.0999

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.188

Alfa AF: 0.133 Hom.: 2232

Bravo AF: 0.162

Asia WGS AF: 0.225 AC: 781 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.5
Dann	Benign	0.64

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: rs2245409; hg19: chr6-24781025;