15-65003115-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139242.4(MTFMT):​c.1117C>T​(p.Pro373Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MTFMT
NM_139242.4 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.113480836).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MTFMTNM_139242.4 linkc.1117C>T p.Pro373Ser missense_variant 9/9 ENST00000220058.9 NP_640335.2 Q96DP5-1
MTFMTXM_005254158.6 linkc.1270C>T p.Pro424Ser missense_variant 9/9 XP_005254215.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MTFMTENST00000220058.9 linkc.1117C>T p.Pro373Ser missense_variant 9/91 NM_139242.4 ENSP00000220058.4 Q96DP5-1
MTFMTENST00000558460.5 linkn.1117C>T non_coding_transcript_exon_variant 9/105 ENSP00000452646.1 Q96DP5-1
MTFMTENST00000560717.5 linkn.*587C>T non_coding_transcript_exon_variant 8/85 ENSP00000457257.1 H3BTN9
MTFMTENST00000560717.5 linkn.*587C>T 3_prime_UTR_variant 8/85 ENSP00000457257.1 H3BTN9

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458742
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725446
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
Cov.:
31
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 26, 2024The c.1117C>T (p.P373S) alteration is located in exon 9 (coding exon 9) of the MTFMT gene. This alteration results from a C to T substitution at nucleotide position 1117, causing the proline (P) at amino acid position 373 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.070
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.84
D
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.72
N
REVEL
Benign
0.033
Sift
Benign
0.12
T
Sift4G
Benign
0.24
T
Polyphen
0.068
B
Vest4
0.10
MutPred
0.33
Loss of glycosylation at P373 (P = 0.0191);
MVP
0.77
MPC
0.12
ClinPred
0.80
D
GERP RS
4.6
Varity_R
0.051
gMVP
0.22

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs921380809; hg19: chr15-65295453; COSMIC: COSV54978258; API