dbSNP rs2754775: GMNN:c.-317G>T (chr6-24774953-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015895.5(GMNN):c.-317G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,322 control chromosomes in the GnomAD database, including 2,010 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2010 hom., cov: 33)

Exomes 𝑓: 0.12 ( 0 hom. )

Consequence

GMNN
NM_015895.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.497

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

Meier-Gorlin syndrome 6
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Meier-Gorlin syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GMNN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GMNN	NM_015895.5 link	c.-317G>T	5_prime_UTR_variant	Exon 1 of 7	ENST00000230056.8	NP_056979.1	O75496A0A024QZY7
GMNN	NM_001251989.2 link	c.-185G>T	5_prime_UTR_variant	Exon 1 of 7		NP_001238918.1	O75496A0A024QZY7
GMNN	NM_001251990.2 link	c.-109G>T	5_prime_UTR_variant	Exon 1 of 7		NP_001238919.1	O75496A0A024QZY7
GMNN	XM_005249159.3 link	c.-897G>T	5_prime_UTR_variant	Exon 1 of 7		XP_005249216.1	O75496A0A024QZY7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GMNN	ENST00000230056.8 link	c.-317G>T	5_prime_UTR_variant	Exon 1 of 7	1	NM_015895.5	ENSP00000230056.3	O75496
GMNN	ENST00000468943.1 link	n.5G>T	non_coding_transcript_exon_variant	Exon 1 of 2	2
GMNN	ENST00000356509.7 link	c.-185G>T	5_prime_UTR_variant	Exon 1 of 7	2		ENSP00000348902.3	O75496

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23269

AN:

152146

Hom.:

2008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.0828

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.185

GnomAD4 exome

AF:

0.121

AC:

AN:

Hom.:

Cov.:

AF XY:

0.140

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0625

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.582

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.153

AC:

23294

AN:

152264

Hom.:

2010

Cov.:

AF XY:

0.153

AC XY:

11361

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.229

AC:

9525

AN:

41536

American (AMR)

AF:

0.146

AC:

2237

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

648

AN:

3472

East Asian (EAS)

AF:

0.109

AC:

564

AN:

5172

South Asian (SAS)

AF:

0.254

AC:

1227

AN:

4828

European-Finnish (FIN)

AF:

0.0828

AC:

880

AN:

10622

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7578

AN:

68008

Other (OTH)

AF:

0.184

AC:

390

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1009

2019

3028

4038

5047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.146

Hom.:

1300

Bravo

AF:

0.159

Asia WGS

AF:

0.226

AC:

785

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.1

(source)

DANN

Benign

0.70

PhyloP100

-0.50

PromoterAI

-0.025

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over