chr15-65003103-T-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_139242.4(MTFMT):ā€‹c.1129A>Cā€‹(p.Lys377Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,610,146 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: š‘“ 0.0011 ( 1 hom., cov: 31)
Exomes š‘“: 0.0018 ( 1 hom. )

Consequence

MTFMT
NM_139242.4 missense

Scores

18

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 1.20
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 Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0066463053).
BP6
Variant 15-65003103-T-G is Benign according to our data. Variant chr15-65003103-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 985377.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1, Benign=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MTFMTNM_139242.4 linkc.1129A>C p.Lys377Gln missense_variant 9/9 ENST00000220058.9 NP_640335.2 Q96DP5-1
MTFMTXM_005254158.6 linkc.1282A>C p.Lys428Gln missense_variant 9/9 XP_005254215.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MTFMTENST00000220058.9 linkc.1129A>C p.Lys377Gln missense_variant 9/91 NM_139242.4 ENSP00000220058.4 Q96DP5-1
MTFMTENST00000558460.5 linkn.1129A>C non_coding_transcript_exon_variant 9/105 ENSP00000452646.1 Q96DP5-1
MTFMTENST00000560717.5 linkn.*599A>C non_coding_transcript_exon_variant 8/85 ENSP00000457257.1 H3BTN9
MTFMTENST00000560717.5 linkn.*599A>C 3_prime_UTR_variant 8/85 ENSP00000457257.1 H3BTN9

Frequencies

GnomAD3 genomes
AF:
0.00105
AC:
160
AN:
152178
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000289
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000590
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00203
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000893
AC:
221
AN:
247374
Hom.:
0
AF XY:
0.000968
AC XY:
130
AN XY:
134230
show subpopulations
Gnomad AFR exome
AF:
0.000518
Gnomad AMR exome
AF:
0.000323
Gnomad ASJ exome
AF:
0.000100
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000166
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00172
Gnomad OTH exome
AF:
0.000500
GnomAD4 exome
AF:
0.00180
AC:
2623
AN:
1457850
Hom.:
1
Cov.:
31
AF XY:
0.00176
AC XY:
1274
AN XY:
724950
show subpopulations
Gnomad4 AFR exome
AF:
0.000360
Gnomad4 AMR exome
AF:
0.000384
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000105
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.00225
Gnomad4 OTH exome
AF:
0.00140
GnomAD4 genome
AF:
0.00105
AC:
160
AN:
152296
Hom.:
1
Cov.:
31
AF XY:
0.00109
AC XY:
81
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00203
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00148
Hom.:
1
Bravo
AF:
0.00112
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.00259
AC:
10
ESP6500AA
AF:
0.00109
AC:
4
ESP6500EA
AF:
0.00134
AC:
11
ExAC
AF:
0.000745
AC:
90

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023MTFMT: BP4 -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 30, 2025- -
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 22, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
15
DANN
Benign
0.87
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.071
N
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.0066
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.42
N
REVEL
Benign
0.058
Sift
Benign
0.56
T
Sift4G
Benign
0.14
T
Polyphen
0.017
B
Vest4
0.097
MVP
0.64
MPC
0.13
ClinPred
0.0037
T
GERP RS
0.90
Varity_R
0.063
gMVP
0.27

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: rs34507711; hg19: chr15-65295441; API