chr6-24780664-A-C

Position:

chr6-24780664-A-C

Variant summary

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

The NM_015895.5(GMNN):c.53A>C(p.Asn18Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 1,551,152 control chromosomes in the GnomAD database, including 12,770 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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 0.089 ( 1601 hom., cov: 32)

Exomes 𝑓: 0.066 ( 11169 hom. )

Consequence

GMNN
NM_015895.5 missense, splice_region

Scores

Splicing: ADA: 0.0001447

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.107

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1263939E-4).

BP6

Variant 6-24780664-A-C is Benign according to our data. Variant chr6-24780664-A-C is described in ClinVar as [Benign]. Clinvar id is 1164494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMNN	NM_015895.5 link	c.53A>C	p.Asn18Thr	missense_variant, splice_region_variant	3/7	ENST00000230056.8	NP_056979.1	O75496A0A024QZY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMNN	ENST00000230056.8 link	c.53A>C	p.Asn18Thr	missense_variant, splice_region_variant	3/7	1	NM_015895.5	ENSP00000230056.3		O75496

Frequencies

GnomAD3 genomes

AF:

0.0891

AC:

13553

AN:

152114

Hom.:

1592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0898

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0310

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0344

Gnomad OTH

AF:

0.0774

GnomAD3 exomes

AF:

0.133

AC:

33408

AN:

250886

Hom.:

6104

AF XY:

0.119

AC XY:

16074

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.0865

Gnomad AMR exome

AF:

0.396

Gnomad ASJ exome

AF:

0.0188

Gnomad EAS exome

AF:

0.542

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.0322

Gnomad NFE exome

AF:

0.0348

Gnomad OTH exome

AF:

0.0891

GnomAD4 exome

AF:

0.0656

AC:

91720

AN:

1398922

Hom.:

11169

Cov.:

AF XY:

0.0647

AC XY:

45286

AN XY:

700042

show subpopulations

Gnomad4 AFR exome

AF:

0.0858

Gnomad4 AMR exome

AF:

0.377

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.550

Gnomad4 SAS exome

AF:

0.0969

Gnomad4 FIN exome

AF:

0.0316

Gnomad4 NFE exome

AF:

0.0338

Gnomad4 OTH exome

AF:

0.0750

GnomAD4 genome

AF:

0.0892

AC:

13576

AN:

152230

Hom.:

1601

Cov.:

AF XY:

0.0956

AC XY:

7116

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0897

Gnomad4 AMR

AF:

0.233

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.543

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.0310

Gnomad4 NFE

AF:

0.0344

Gnomad4 OTH

AF:

0.0791

Alfa

AF:

0.0544

Hom.:

1582

Bravo

AF:

0.106

TwinsUK

AF:

0.0334

AC:

124

ALSPAC

AF:

0.0371

AC:

143

ESP6500AA

AF:

0.0819

AC:

361

ESP6500EA

AF:

0.0343

AC:

295

ExAC

AF:

0.121

AC:

14654

Asia WGS

AF:

0.270

AC:

938

AN:

3478

EpiCase

AF:

0.0324

EpiControl

AF:

0.0341

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

GMNN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.4

DANN

Benign

0.95

DEOGEN2

Benign

0.068

T;T;.;T;T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.45

.;.;T;T;T;T

MetaRNN

Benign

0.00011

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M;.;M;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.88

N;N;N;.;N;N

REVEL

Benign

0.062

Sift

Benign

0.16

T;T;T;.;T;T

Sift4G

Benign

0.46

T;T;T;T;D;T

Polyphen

0.71

P;P;.;P;.;.

Vest4

0.076

MPC

0.32

ClinPred

0.042

GERP RS

-0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.010

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

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