Variant 6-24780716-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015895.5(GMNN):c.105A>C(p.Gly35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,588,916 control chromosomes in the GnomAD database, including 1,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 129 hom., cov: 33)

Exomes 𝑓: 0.044 ( 1662 hom. )

Consequence

GMNN
NM_015895.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.06

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-24780716-A-C is Benign according to our data. Variant chr6-24780716-A-C is described in ClinVar as [Benign]. Clinvar id is 1168949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMNN	NM_015895.5 linkuse as main transcript	c.105A>C	p.Gly35=	synonymous_variant	3/7	ENST00000230056.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMNN	ENST00000230056.8 linkuse as main transcript	c.105A>C	p.Gly35=	synonymous_variant	3/7	1	NM_015895.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0351

AC:

5336

AN:

152180

Hom.:

129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00927

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0407

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0407

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0548

Gnomad OTH

AF:

0.0288

GnomAD3 exomes

AF:

0.0337

AC:

8470

AN:

251288

Hom.:

223

AF XY:

0.0335

AC XY:

4557

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00800

Gnomad AMR exome

AF:

0.0280

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00526

Gnomad FIN exome

AF:

0.0404

Gnomad NFE exome

AF:

0.0525

Gnomad OTH exome

AF:

0.0342

GnomAD4 exome

AF:

0.0437

AC:

62807

AN:

1436618

Hom.:

1662

Cov.:

AF XY:

0.0428

AC XY:

30624

AN XY:

716264

show subpopulations

Gnomad4 AFR exome

AF:

0.00624

Gnomad4 AMR exome

AF:

0.0292

Gnomad4 ASJ exome

AF:

0.0160

Gnomad4 EAS exome

AF:

0.000228

Gnomad4 SAS exome

AF:

0.00506

Gnomad4 FIN exome

AF:

0.0410

Gnomad4 NFE exome

AF:

0.0516

Gnomad4 OTH exome

AF:

0.0343

GnomAD4 genome

AF:

0.0350

AC:

5336

AN:

152298

Hom.:

129

Cov.:

AF XY:

0.0341

AC XY:

2538

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00924

Gnomad4 AMR

AF:

0.0407

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.0407

Gnomad4 NFE

AF:

0.0548

Gnomad4 OTH

AF:

0.0285

Alfa

AF:

0.0473

Hom.:

257

Bravo

AF:

0.0333

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0448

EpiControl

AF:

0.0487

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.9

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over