NM_199227.3:c.*1181T>G

Variant names:

• chr2-172081587-T-G
• rs788160
• NM_199227.3:c.*1181T>G

Variant summary

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

The NM_199227.3(METAP1D):​c.*1181T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,192 control chromosomes in the GnomAD database, including 52,199 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 0.83 (52189 hom., cov: 33)
  • Exomes 𝑓: 0.82 (10 hom.)
• Consequence: METAP1D NM_199227.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430
• Publications: 9 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METAP1D	NM_199227.3	c.*1181T>G		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.*1181T>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_199227.3	ENSP00000315152.4

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125854 AN: 152046 Hom.: 52155 Cov.: 33

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.831

GnomAD4 exome AF: 0.821 AC: 23 AN: 28 Hom.: 10 Cov.: 0 AF XY: 0.792 AC XY: 19 AN XY: 24

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) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.818 AC: 18 AN: 22

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.828 AC: 125944 AN: 152164 Hom.: 52189 Cov.: 33 AF XY: 0.828 AC XY: 61617 AN XY: 74394

African (AFR) AF: 0.844 AC: 35036 AN: 41508

American (AMR) AF: 0.836 AC: 12770 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3472

East Asian (EAS) AF: 0.897 AC: 4630 AN: 5162

South Asian (SAS) AF: 0.859 AC: 4151 AN: 4830

European-Finnish (FIN) AF: 0.818 AC: 8666 AN: 10596

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54831 AN: 68000

Other (OTH) AF: 0.832 AC: 1755 AN: 2110

Alfa AF: 0.810 Hom.: 19828

Bravo AF: 0.831

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.41
PhyloP100		0.43
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: rs788160; hg19: chr2-172946315;