Variant 6-24781491-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015895.5(GMNN):c.144G>C(p.Leu48Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,596,746 control chromosomes in the GnomAD database, including 2,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.072 ( 1145 hom., cov: 32)

Exomes 𝑓: 0.014 ( 1080 hom. )

Consequence

GMNN
NM_015895.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.273

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004207343).

BP6

Variant 6-24781491-G-C is Benign according to our data. Variant chr6-24781491-G-C is described in ClinVar as [Benign]. Clinvar id is 1165184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 link	c.144G>C	p.Leu48Phe	missense_variant	4/7	ENST00000230056.8	NP_056979.1	O75496A0A024QZY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMNN	ENST00000230056.8 link	c.144G>C	p.Leu48Phe	missense_variant	4/7	1	NM_015895.5	ENSP00000230056.3		O75496

Frequencies

GnomAD3 genomes

AF:

0.0717

AC:

10897

AN:

152030

Hom.:

1138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.0372

Gnomad SAS

AF:

0.0462

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00509

Gnomad OTH

AF:

0.0752

GnomAD3 exomes

AF:

0.0274

AC:

6849

AN:

249596

Hom.:

453

AF XY:

0.0246

AC XY:

3327

AN XY:

134994

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.0232

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.0297

Gnomad SAS exome

AF:

0.0389

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00522

Gnomad OTH exome

AF:

0.0223

GnomAD4 exome

AF:

0.0138

AC:

19948

AN:

1444598

Hom.:

1080

Cov.:

AF XY:

0.0140

AC XY:

10063

AN XY:

718824

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.0246

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.0419

Gnomad4 SAS exome

AF:

0.0399

Gnomad4 FIN exome

AF:

0.000603

Gnomad4 NFE exome

AF:

0.00413

Gnomad4 OTH exome

AF:

0.0270

GnomAD4 genome

AF:

0.0718

AC:

10926

AN:

152148

Hom.:

1145

Cov.:

AF XY:

0.0699

AC XY:

5196

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.0409

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.0374

Gnomad4 SAS

AF:

0.0456

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00509

Gnomad4 OTH

AF:

0.0820

Alfa

AF:

0.0171

Hom.:

142

Bravo

AF:

0.0829

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.220

AC:

969

ESP6500EA

AF:

0.00698

AC:

ExAC

AF:

0.0343

AC:

4159

Asia WGS

AF:

0.0670

AC:

234

AN:

3478

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;T;.;T;T;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.67

.;.;T;T;T;T

MetaRNN

Benign

0.0042

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;M;.;M;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

N;N;N;.;N;N

REVEL

Benign

0.12

Sift

Benign

0.089

T;T;T;.;T;T

Sift4G

Benign

0.070

T;T;T;T;T;T

Polyphen

0.93

P;P;.;P;.;.

Vest4

0.062

MutPred

0.17

Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);

MPC

0.54

ClinPred

0.030

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.028

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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