NM_199227.3:c.296A>G

Variant names:

• chr2-172063808-A-G
• NM_199227.3:c.296A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199227.3(METAP1D):​c.296A>G​(p.Gln99Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: METAP1D NM_199227.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19373113).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METAP1D	NM_199227.3	MANE Select	c.296A>G	p.Gln99Arg	missense	Exon 3 of 10	NP_954697.1	Q6UB28
	METAP1D	NM_001322278.2		c.-145A>G		5_prime_UTR	Exon 3 of 10	NP_001309207.1
	METAP1D	NM_001322279.2		c.-59A>G		5_prime_UTR	Exon 3 of 10	NP_001309208.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METAP1D	ENST00000315796.5	TSL:1 MANE Select	c.296A>G	p.Gln99Arg	missense	Exon 3 of 10	ENSP00000315152.4	Q6UB28
	METAP1D	ENST00000913778.1		c.398A>G	p.Gln133Arg	missense	Exon 4 of 11	ENSP00000583837.1
	METAP1D	ENST00000913779.1		c.356A>G	p.Gln119Arg	missense	Exon 4 of 11	ENSP00000583838.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.032
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.025	N
PhyloP100		3.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.18
Sift	Benign	0.53	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.49		Gain of catalytic residue at Q99 (P = 0.0415)
MVP		0.60
MPC		0.15
ClinPred		0.76	D
GERP RS		4.5
Varity_R		0.22
gMVP		0.63
Mutation Taster		=91/9	polymorphism

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

hg19: chr2-172928536;