chr6-24781011-G-C

Position:

• chr6-24781011-G-C

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+271G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,064 control chromosomes in the GnomAD database, including 1,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.072 (1151 hom., cov: 32)
• Consequence: GMNN NM_015895.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.981

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=-0.95).
• BP6: Variant 6-24781011-G-C is Benign according to our data. Variant chr6-24781011-G-C is described in ClinVar as [Benign]. Clinvar id is 1226415.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMNN	NM_015895.5	c.129+271G>C		intron_variant		ENST00000230056.8	NP_056979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMNN	ENST00000230056.8	c.129+271G>C		intron_variant		1	NM_015895.5	ENSP00000230056.3

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10872 AN: 151946 Hom.: 1144 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.0463

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00507

Gnomad OTH AF: 0.0747

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

GnomAD4 genome AF: 0.0717 AC: 10901 AN: 152064 Hom.: 1151 Cov.: 32 AF XY: 0.0697 AC XY: 5183 AN XY: 74342

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.0374

Gnomad4 SAS AF: 0.0457

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.00507

Gnomad4 OTH AF: 0.0815

Alfa AF: 0.0430 Hom.: 86

Bravo AF: 0.0829

Asia WGS AF: 0.0670 AC: 234 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.0
DANN	Benign	0.73

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: rs9467311; hg19: chr6-24781239; COSMIC: COSV57776571; COSMIC: COSV57776571;