15-65003115-G-C

Variant names:

• chr15-65003115-G-C
• rs921380809
• NM_139242.4:c.1117C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139242.4(MTFMT):​c.1117C>G​(p.Pro373Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: MTFMT NM_139242.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

Genes affected

MTFMT (HGNC:29666): (mitochondrial methionyl-tRNA formyltransferase) The protein encoded by this nuclear gene localizes to the mitochondrion, where it catalyzes the formylation of methionyl-tRNA. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11438048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTFMT	NM_139242.4	c.1117C>G	p.Pro373Ala	missense_variant	Exon 9 of 9	ENST00000220058.9	NP_640335.2
MTFMT	XM_005254158.6	c.1270C>G	p.Pro424Ala	missense_variant	Exon 9 of 9		XP_005254215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTFMT	ENST00000220058.9	c.1117C>G	p.Pro373Ala	missense_variant	Exon 9 of 9	1	NM_139242.4	ENSP00000220058.4
MTFMT	ENST00000558460.5	n.1117C>G		non_coding_transcript_exon_variant	Exon 9 of 10	5		ENSP00000452646.1
MTFMT	ENST00000560717.5	n.*587C>G		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000457257.1
MTFMT	ENST00000560717.5	n.*587C>G		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000457257.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247294 Hom.: 0 AF XY: 0.00000745 AC XY: 1 AN XY: 134144

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1458742 Hom.: 0 Cov.: 31 AF XY: 0.00000965 AC XY: 7 AN XY: 725446

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000901

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.064
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.044
Sift	Benign	0.088	T
Sift4G	Benign	0.19	T
Polyphen		0.010	B
Vest4		0.14
MutPred		0.34		Loss of glycosylation at P373 (P = 0.0059);
MVP		0.77
MPC		0.11
ClinPred		0.38	T
GERP RS		4.6
Varity_R		0.042
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs921380809; hg19: chr15-65295453;