2-172081799-T-C

Variant names:

• chr2-172081799-T-C
• rs1047889
• NM_199227.3:c.*1393T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515
• Publications: 7 publications found

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]

ENSG00000288958 (HGNC:):

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METAP1D	NM_199227.3	c.*1393T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000315796.5	NP_954697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METAP1D	ENST00000315796.5	c.*1393T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_199227.3	ENSP00000315152.4
ENSG00000288958	ENST00000688295.1	n.*191A>G		downstream_gene_variant
ENSG00000288958	ENST00000715284.1	n.*191A>G		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63315 AN: 151918 Hom.: 13795 Cov.: 32

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: 10 AN: 18 Hom.: 3 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.583 AC: 7 AN: 12

Other (OTH) AF: 0.500 AC: 3 AN: 6

GnomAD4 genome AF: 0.417 AC: 63346 AN: 152036 Hom.: 13803 Cov.: 32 AF XY: 0.428 AC XY: 31776 AN XY: 74312

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1047889; hg19: chr2-172946527;