1-25823671-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001099625.2(MTFR1L):​c.52C>T​(p.His18Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

MTFR1L
NM_001099625.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81
Variant links:
Genes affected
MTFR1L (HGNC:28836): (mitochondrial fission regulator 1 like) Predicted to be involved in aerobic respiration and mitochondrial fission. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.040049374).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTFR1LNM_001099625.2 linkc.52C>T p.His18Tyr missense_variant Exon 3 of 7 ENST00000374303.7 NP_001093095.1 Q9H019-1A0A0S2Z5H6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTFR1LENST00000374303.7 linkc.52C>T p.His18Tyr missense_variant Exon 3 of 7 1 NM_001099625.2 ENSP00000363421.2 Q9H019-1
ENSG00000255054ENST00000527604.1 linkn.*129C>T non_coding_transcript_exon_variant Exon 4 of 4 5 ENSP00000457066.1 H3BT81
ENSG00000255054ENST00000527604.1 linkn.*129C>T 3_prime_UTR_variant Exon 4 of 4 5 ENSP00000457066.1 H3BT81

Frequencies

GnomAD3 genomes
AF:
0.000263
AC:
40
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
GnomAD3 exomes
AF:
0.0000601
AC:
15
AN:
249514
Hom.:
0
AF XY:
0.0000443
AC XY:
6
AN XY:
135372
show subpopulations
Gnomad AFR exome
AF:
0.000969
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:
0.0000178
AC:
26
AN:
1461788
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.000777
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:
0.00
GnomAD4 genome
AF:
0.000263
AC:
40
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.000255
AC XY:
19
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.000963
Gnomad4 AMR
AF:
0.00
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:
0.00
Alfa
AF:
0.000225
Hom.:
0
Bravo
AF:
0.000283
ESP6500AA
AF:
0.000244
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000827
AC:
10

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.52C>T (p.H18Y) alteration is located in exon 3 (coding exon 2) of the MTFR1L gene. This alteration results from a C to T substitution at nucleotide position 52, causing the histidine (H) at amino acid position 18 to be replaced by a tyrosine (Y). 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
0.11
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.012
.;T;T;.;.;.;T;T;T;T;.
Eigen
Benign
0.054
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.85
T;D;D;.;T;D;D;.;D;.;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.040
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.77
.;N;.;N;.;N;.;N;.;N;N
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
2.4
N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.25
Sift
Benign
1.0
T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.99, 1.0, 0.99
.;D;.;D;.;D;.;D;.;D;D
Vest4
0.43, 0.44, 0.43, 0.46, 0.43
MVP
0.15
MPC
0.35
ClinPred
0.087
T
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.054
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs34450889; hg19: chr1-26150162; API