Variant 12-95512827-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_006838.4(METAP2):c.1095C>A(p.Thr365Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0865 in 1,606,536 control chromosomes in the GnomAD database, including 6,544 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 0.094 ( 705 hom., cov: 31)

Exomes 𝑓: 0.086 ( 5839 hom. )

Consequence

METAP2
NM_006838.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.356

Variant links:

Genes affected

METAP2 (HGNC:16672): (methionyl aminopeptidase 2) The protein encoded by this gene is a member of the methionyl aminopeptidase family. The encoded protein functions both by protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation and by removing the amino-terminal methionine residue from nascent proteins. Increased expression of this gene is associated with various forms of cancer, and the anti-cancer drugs fumagillin and ovalicin inhibit the protein by irreversibly binding to its active site. Inhibitors of this gene have also been shown to be effective for the treatment of obesity. A pseudogene of this gene is located on chromosome 2. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

METAP2 links:

METAP2 (HGNC:):

METAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP7

Synonymous conserved (PhyloP=-0.356 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METAP2	NM_006838.4 linkuse as main transcript	c.1095C>A	p.Thr365Thr	synonymous_variant	10/11	ENST00000323666.10	NP_006829.1	P50579-1A0A140VJE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METAP2	ENST00000323666.10 linkuse as main transcript	c.1095C>A	p.Thr365Thr	synonymous_variant	10/11	1	NM_006838.4	ENSP00000325312.5		P50579-1

Frequencies

GnomAD3 genomes

AF:

0.0939

AC:

14270

AN:

151914

Hom.:

709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.119

Gnomad AMR

AF:

0.0739

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.0830

Gnomad FIN

AF:

0.0654

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.0891

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.0940

AC:

23510

AN:

250120

Hom.:

1305

AF XY:

0.0927

AC XY:

12537

AN XY:

135224

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0821

Gnomad ASJ exome

AF:

0.110

Gnomad EAS exome

AF:

0.195

Gnomad SAS exome

AF:

0.0698

Gnomad FIN exome

AF:

0.0686

Gnomad NFE exome

AF:

0.0899

Gnomad OTH exome

AF:

0.0996

GnomAD4 exome

AF:

0.0857

AC:

124720

AN:

1454504

Hom.:

5839

Cov.:

AF XY:

0.0859

AC XY:

62147

AN XY:

723828

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.0824

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.0696

Gnomad4 FIN exome

AF:

0.0713

Gnomad4 NFE exome

AF:

0.0823

Gnomad4 OTH exome

AF:

0.0949

GnomAD4 genome

AF:

0.0938

AC:

14265

AN:

152032

Hom.:

705

Cov.:

AF XY:

0.0937

AC XY:

6958

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.0736

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.196

Gnomad4 SAS

AF:

0.0816

Gnomad4 FIN

AF:

0.0654

Gnomad4 NFE

AF:

0.0891

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0916

Hom.:

1594

Bravo

AF:

0.0966

Asia WGS

AF:

0.155

AC:

539

AN:

3478

EpiCase

AF:

0.0970

EpiControl

AF:

0.101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

6.3

DANN

Benign

0.75

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over