6-24777296-AG-GA

Variant names:

• chr6-24777296-AG-GA
• NM_015895.5:c.50_51delAGinsGA
• GMNN p.Lys17Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015895.5(GMNN):​c.50_51delAGinsGA​(p.Lys17Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GMNN NM_015895.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 0 publications found

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]

GMNN Gene-Disease associations (from GenCC):

• Meier-Gorlin syndrome 6

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Meier-Gorlin syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015895.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMNN	NM_015895.5	MANE Select	c.50_51delAGinsGA	p.Lys17Arg	missense splice_region	N/A	NP_056979.1	O75496
	GMNN	NM_001251989.2		c.50_51delAGinsGA	p.Lys17Arg	missense splice_region	N/A	NP_001238918.1	O75496
	GMNN	NM_001251990.2		c.50_51delAGinsGA	p.Lys17Arg	missense splice_region	N/A	NP_001238919.1	O75496

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMNN	ENST00000230056.8	TSL:1 MANE Select	c.50_51delAGinsGA	p.Lys17Arg	missense splice_region	N/A	ENSP00000230056.3	O75496
	GMNN	ENST00000931913.1		c.50_51delAGinsGA	p.Lys17Arg	missense splice_region	N/A	ENSP00000601972.1
	GMNN	ENST00000356509.7	TSL:2	c.50_51delAGinsGA	p.Lys17Arg	missense splice_region	N/A	ENSP00000348902.3	O75496

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-24777524;