Variant chr2-172070935-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000315796.5(METAP1D):c.569C>A(p.Thr190Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

METAP1D
ENST00000315796.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

Variant links:

Genes affected

METAP1D (HGNC:32583): (methionyl aminopeptidase type 1D, mitochondrial) The N-terminal methionine excision pathway is an essential process in which the N-terminal methionine is removed from many proteins, thus facilitating subsequent protein modification. In mitochondria, enzymes that catalyze this reaction are celled methionine aminopeptidases (MetAps, or MAPs; EC 3.4.11.18) (Serero et al., 2003 [PubMed 14532271]).[supplied by OMIM, Mar 2008]

METAP1D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.864

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METAP1D	NM_199227.3 linkuse as main transcript	c.569C>A	p.Thr190Asn	missense_variant	6/10	ENST00000315796.5	NP_954697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
METAP1D	ENST00000315796.5 linkuse as main transcript	c.569C>A	p.Thr190Asn	missense_variant	6/10	1	NM_199227.3	ENSP00000315152	P1
METAP1D	ENST00000392582.2 linkuse as main transcript	n.221C>A		non_coding_transcript_exon_variant	3/4	5
METAP1D	ENST00000468537.1 linkuse as main transcript	n.273C>A		non_coding_transcript_exon_variant	1/4	2
METAP1D	ENST00000488581.5 linkuse as main transcript	n.305C>A		non_coding_transcript_exon_variant	4/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460248

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726412

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

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 26, 2024

The c.569C>A (p.T190N) alteration is located in exon 6 (coding exon 6) of the METAP1D gene. This alteration results from a C to A substitution at nucleotide position 569, causing the threonine (T) at amino acid position 190 to be replaced by an asparagine (N). 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

0.34

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.80

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

0.026

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.63

Sift

Benign

0.032

Sift4G

Uncertain

0.027

Polyphen

0.97

Vest4

0.92

MutPred

0.62

Gain of sheet (P = 0.1208);

MVP

0.72

MPC

0.67

ClinPred

0.98

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.67

gMVP

0.90

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