Variant chr3-190857871-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001146686.3(GMNC):c.296A>T(p.Glu99Val) variant causes a missense change. The variant allele was found at a frequency of 0.000669 in 1,549,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E99K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 0 hom. )

Consequence

GMNC
NM_001146686.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.53

Variant links:

Genes affected

GMNC (HGNC:40049): (geminin coiled-coil domain containing) Predicted to enable chromatin binding activity. Predicted to be involved in DNA replication; negative regulation of DNA replication; and negative regulation of cell cycle. Predicted to act upstream of or within cilium assembly. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GMNC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMNC	NM_001146686.3 linkuse as main transcript	c.296A>T	p.Glu99Val	missense_variant	4/5	ENST00000442080.6
GMNC	XR_924161.3 linkuse as main transcript	n.375A>T		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GMNC	ENST00000442080.6 linkuse as main transcript	c.296A>T	p.Glu99Val	missense_variant	4/5	5	NM_001146686.3	P1
GMNC	ENST00000495042.1 linkuse as main transcript	n.190A>T		non_coding_transcript_exon_variant	1/2	1
GMNC	ENST00000479491.5 linkuse as main transcript	n.202A>T		non_coding_transcript_exon_variant	3/4	4
GMNC	ENST00000456552.1 linkuse as main transcript	c.*179A>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000419

AC:

AN:

157540

Hom.:

AF XY:

0.000492

AC XY:

AN XY:

83262

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000809

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000830

Gnomad NFE exome

AF:

0.000735

Gnomad OTH exome

AF:

0.000675

GnomAD4 exome

AF:

0.000695

AC:

971

AN:

1397670

Hom.:

Cov.:

AF XY:

0.000701

AC XY:

483

AN XY:

689498

show subpopulations

Gnomad4 AFR exome

AF:

0.0000951

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.000815

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000434

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000680

Hom.:

Bravo

AF:

0.000374

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000316

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.296A>T (p.E99V) alteration is located in exon 4 (coding exon 4) of the GMNC gene. This alteration results from a A to T substitution at nucleotide position 296, causing the glutamic acid (E) at amino acid position 99 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.49

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-6.3

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.74

MVP

0.24

ClinPred

0.45

GERP RS

5.9

Varity_R

0.81

gMVP

0.41

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

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