rs7606918

Variant names:

• chr2-172030546-A-G
• rs7606918
• NM_199227.3:c.40+30537A>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.40+30537A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,128 control chromosomes in the GnomAD database, including 2,145 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 0.16 (2145 hom., cov: 32)
• Consequence: METAP1D NM_199227.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METAP1D	NM_199227.3	c.40+30537A>G		intron_variant	Intron 1 of 9	ENST00000315796.5	NP_954697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METAP1D	ENST00000315796.5	c.40+30537A>G		intron_variant	Intron 1 of 9	1	NM_199227.3	ENSP00000315152.4
METAP1D	ENST00000491440.1	n.69+8679A>G		intron_variant	Intron 1 of 2	3
METAP1D	ENST00000493035.5	n.67+30537A>G		intron_variant	Intron 1 of 2	2
METAP1D	ENST00000493742.1	n.55+30537A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24679 AN: 152010 Hom.: 2145 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0349

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24677 AN: 152128 Hom.: 2145 Cov.: 32 AF XY: 0.157 AC XY: 11670 AN XY: 74380

African (AFR) AF: 0.216 AC: 8963 AN: 41456

American (AMR) AF: 0.155 AC: 2371 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3466

East Asian (EAS) AF: 0.122 AC: 631 AN: 5178

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4832

European-Finnish (FIN) AF: 0.114 AC: 1207 AN: 10598

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10238 AN: 67998

Other (OTH) AF: 0.164 AC: 346 AN: 2110

Alfa AF: 0.157 Hom.: 2996

Bravo AF: 0.172

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.68
PhyloP100		0.18
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: rs7606918; hg19: chr2-172895449;