Genetic Variant METAP1D:c.*1393T>C (chr2-172081799-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_199227.3(METAP1D):c.*1393T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,054 control chromosomes in the GnomAD database, including 13,806 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 0.42 ( 13803 hom., cov: 32)

Exomes 𝑓: 0.56 ( 3 hom. )

Consequence

METAP1D
NM_199227.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

Publications

7 publications found

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:

ENSG00000288958 (HGNC:58943):

ENSG00000288958 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=-0.56).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199227.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
METAP1D	NM_199227.3	MANE Select	c.*1393T>C	3_prime_UTR	Exon 10 of 10	NP_954697.1	Q6UB28
METAP1D	NM_001322278.2		c.*1393T>C	3_prime_UTR	Exon 10 of 10	NP_001309207.1
METAP1D	NM_001322279.2		c.*1393T>C	3_prime_UTR	Exon 10 of 10	NP_001309208.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
METAP1D	ENST00000315796.5	TSL:1 MANE Select	c.*1393T>C	3_prime_UTR	Exon 10 of 10	ENSP00000315152.4	Q6UB28
METAP1D	ENST00000913778.1		c.*1393T>C	3_prime_UTR	Exon 11 of 11	ENSP00000583837.1
METAP1D	ENST00000903316.1		c.*1393T>C	3_prime_UTR	Exon 9 of 9	ENSP00000573375.1

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63315

AN:

151918

Hom.:

13795

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.417

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.390

GnomAD4 exome

AF:

0.556

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.583

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.417

AC:

63346

AN:

152036

Hom.:

13803

Cov.:

AF XY:

0.428

AC XY:

31776

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.313

AC:

12970

AN:

41470

American (AMR)

AF:

0.418

AC:

6378

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1359

AN:

3466

East Asian (EAS)

AF:

0.613

AC:

3179

AN:

5182

South Asian (SAS)

AF:

0.540

AC:

2608

AN:

4826

European-Finnish (FIN)

AF:

0.581

AC:

6123

AN:

10540

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.431

AC:

29277

AN:

67974

Other (OTH)

AF:

0.390

AC:

823

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1892

3785

5677

7570

9462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.410

Hom.:

19069

Bravo

AF:

0.397

Asia WGS

AF:

0.540

AC:

1880

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.52

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over