6-24781239-A-AAAT

Position:

• chr6-24781239-A-AAAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015895.5(GMNN):​c.130-234_130-232dupAAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 151,986 control chromosomes in the GnomAD database, including 1,133 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.072 (1133 hom., cov: 31)
• Consequence: GMNN NM_015895.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.441

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 -10 ACMG points.

• BP6: Variant 6-24781239-A-AAAT is Benign according to our data. Variant chr6-24781239-A-AAAT is described in ClinVar as [Benign]. Clinvar id is 1272077.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMNN	NM_015895.5	c.130-234_130-232dupAAT		intron_variant		ENST00000230056.8	NP_056979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMNN	ENST00000230056.8	c.130-238_130-237insAAT		intron_variant		1	NM_015895.5	ENSP00000230056.3

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10843 AN: 151870 Hom.: 1126 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.00105

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.00506

Gnomad OTH AF: 0.0747

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

GnomAD4 genome AF: 0.0715 AC: 10871 AN: 151986 Hom.: 1133 Cov.: 31 AF XY: 0.0695 AC XY: 5164 AN XY: 74346

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.0406

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.0374

Gnomad4 SAS AF: 0.0459

Gnomad4 FIN AF: 0.00105

Gnomad4 NFE AF: 0.00506

Gnomad4 OTH AF: 0.0815

Alfa AF: 0.0445 Hom.: 39

Asia WGS AF: 0.0650 AC: 228 AN: 3466

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

Jun 20, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59071900; hg19: chr6-24781467;