NM_015942.5:c.643A>G

Variant summary

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

The NM_015942.5(MTERF3):​c.643A>G​(p.Ile215Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,609,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MTERF3
NM_015942.5 missense

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71
Variant links:
Genes affected
MTERF3 (HGNC:24258): (mitochondrial transcription termination factor 3) Enables transcription cis-regulatory region binding activity. Involved in negative regulation of transcription, DNA-templated. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

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=0.24802926).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTERF3NM_015942.5 linkc.643A>G p.Ile215Val missense_variant Exon 4 of 8 ENST00000287025.4 NP_057026.3 Q96E29-1
MTERF3NM_001286643.1 linkc.643A>G p.Ile215Val missense_variant Exon 4 of 9 NP_001273572.1 E5RIK9
MTERF3NM_001362964.1 linkc.73A>G p.Ile25Val missense_variant Exon 4 of 8 NP_001349893.1
MTERF3XM_011517054.3 linkc.304A>G p.Ile102Val missense_variant Exon 4 of 8 XP_011515356.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTERF3ENST00000287025.4 linkc.643A>G p.Ile215Val missense_variant Exon 4 of 8 1 NM_015942.5 ENSP00000287025.3 Q96E29-1
MTERF3ENST00000523821.5 linkc.643A>G p.Ile215Val missense_variant Exon 4 of 9 1 ENSP00000429400.1 E5RIK9
MTERF3ENST00000522822.5 linkc.280A>G p.Ile94Val missense_variant Exon 2 of 6 2 ENSP00000430138.1 Q96E29-3
MTERF3ENST00000524341.5 linkc.73A>G p.Ile25Val missense_variant Exon 2 of 5 3 ENSP00000429267.1 E5RIY4

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
151990
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000243
AC:
6
AN:
246528
Hom.:
0
AF XY:
0.0000300
AC XY:
4
AN XY:
133256
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000554
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000444
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000549
AC:
8
AN:
1457248
Hom.:
0
Cov.:
31
AF XY:
0.00000828
AC XY:
6
AN XY:
724800
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
151990
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.643A>G (p.I215V) alteration is located in exon 4 (coding exon 3) of the MTERF3 gene. This alteration results from a A to G substitution at nucleotide position 643, causing the isoleucine (I) at amino acid position 215 to be replaced by a valine (V). 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
0.083
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
.;.;.;T
Eigen
Uncertain
0.22
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.70
T;T;T;T
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.25
T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.85
N;N;N;N
REVEL
Benign
0.18
Sift
Uncertain
0.012
D;T;T;T
Sift4G
Uncertain
0.028
D;D;T;D
Polyphen
0.97
D;.;.;D
Vest4
0.37
MutPred
0.55
Loss of catalytic residue at L220 (P = 0.061);.;.;Loss of catalytic residue at L220 (P = 0.061);
MVP
0.29
MPC
0.034
ClinPred
0.16
T
GERP RS
3.6
Varity_R
0.082
gMVP
0.36

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: rs749363533; hg19: chr8-97263168; API