15-65029598-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBS1BS2

The NM_139242.4(MTFMT):ā€‹c.16C>Gā€‹(p.Arg6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,429,532 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6P) has been classified as Likely pathogenic.

Frequency

Genomes: š‘“ 0.0023 ( 2 hom., cov: 32)
Exomes š‘“: 0.00018 ( 1 hom. )

Consequence

MTFMT
NM_139242.4 missense

Scores

2
1
15

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.40
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 Benign. Variant got -18 ACMG points.

PM5
Other missense variant is known to change same aminoacid residue: Variant chr15-65029597-C-G is described in Lovd as [Likely_pathogenic].
BP4
Computational evidence support a benign effect (MetaRNN=0.006596297).
BP6
Variant 15-65029598-G-C is Benign according to our data. Variant chr15-65029598-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 669075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0023 (350/151986) while in subpopulation AFR AF= 0.00814 (338/41534). AF 95% confidence interval is 0.00742. There are 2 homozygotes in gnomad4. There are 169 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MTFMTNM_139242.4 linkc.16C>G p.Arg6Gly missense_variant 1/9 ENST00000220058.9 NP_640335.2 Q96DP5-1
MTFMTXM_005254158.6 linkc.16C>G p.Arg6Gly missense_variant 1/9 XP_005254215.2
MTFMTXR_001751081.2 linkn.42C>G non_coding_transcript_exon_variant 1/5
MTFMTXR_007064421.1 linkn.42C>G non_coding_transcript_exon_variant 1/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MTFMTENST00000220058.9 linkc.16C>G p.Arg6Gly missense_variant 1/91 NM_139242.4 ENSP00000220058.4 Q96DP5-1

Frequencies

GnomAD3 genomes
AF:
0.00229
AC:
348
AN:
151876
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00811
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.0000833
AC:
6
AN:
72046
Hom.:
0
AF XY:
0.0000720
AC XY:
3
AN XY:
41690
show subpopulations
Gnomad AFR exome
AF:
0.00683
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000180
AC:
230
AN:
1277546
Hom.:
1
Cov.:
32
AF XY:
0.000157
AC XY:
98
AN XY:
625938
show subpopulations
Gnomad4 AFR exome
AF:
0.00797
Gnomad4 AMR exome
AF:
0.0000414
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000143
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.81e-7
Gnomad4 OTH exome
AF:
0.000405
GnomAD4 genome
AF:
0.00230
AC:
350
AN:
151986
Hom.:
2
Cov.:
32
AF XY:
0.00227
AC XY:
169
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.00814
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.0000788
Hom.:
1
Bravo
AF:
0.00252
ExAC
AF:
0.0000448
AC:
3

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 17, 2024- -
Likely benign, criteria provided, single submitterclinical testingGeneDxJan 13, 2020- -
MTFMT-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 05, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
15
DANN
Benign
0.89
DEOGEN2
Benign
0.19
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.25
N
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.0066
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.7
L
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.91
N
REVEL
Benign
0.28
Sift
Uncertain
0.020
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.0060
B
Vest4
0.37
MVP
0.52
MPC
0.21
ClinPred
0.015
T
GERP RS
0.48
Varity_R
0.077
gMVP
0.57

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: rs199599204; hg19: chr15-65321936; API