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GeneBe

8-96256985-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015942.5(MTERF3):c.464C>G(p.Thr155Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,612,948 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

MTERF3
NM_015942.5 missense

Scores

5
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.28
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MTERF3NM_015942.5 linkuse as main transcriptc.464C>G p.Thr155Ser missense_variant 3/8 ENST00000287025.4
MTERF3NM_001286643.1 linkuse as main transcriptc.464C>G p.Thr155Ser missense_variant 3/9
MTERF3XM_011517054.3 linkuse as main transcriptc.125C>G p.Thr42Ser missense_variant 3/8
MTERF3NM_001362964.1 linkuse as main transcriptc.-107C>G 5_prime_UTR_variant 3/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MTERF3ENST00000287025.4 linkuse as main transcriptc.464C>G p.Thr155Ser missense_variant 3/81 NM_015942.5 P1Q96E29-1
MTERF3ENST00000523821.5 linkuse as main transcriptc.464C>G p.Thr155Ser missense_variant 3/91
MTERF3ENST00000522822.5 linkuse as main transcriptc.101C>G p.Thr34Ser missense_variant 1/62 Q96E29-3
MTERF3ENST00000524341.5 linkuse as main transcriptc.-107C>G 5_prime_UTR_variant 1/53

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152192
Hom.:
0
Cov.:
32
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:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
249958
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135068
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000530
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000787
AC:
115
AN:
1460638
Hom.:
0
Cov.:
30
AF XY:
0.0000606
AC XY:
44
AN XY:
726582
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
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:
0.0000954
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152310
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74490
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:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000680
ExAC
AF:
0.0000412
AC:
5
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 08, 2023The c.464C>G (p.T155S) alteration is located in exon 3 (coding exon 2) of the MTERF3 gene. This alteration results from a C to G substitution at nucleotide position 464, causing the threonine (T) at amino acid position 155 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.10
Cadd
Uncertain
24
Dann
Uncertain
1.0
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.94
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Benign
0.0097
T
MetaRNN
Uncertain
0.63
D;D;D
MetaSVM
Benign
-1.2
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.4
D;D;D
REVEL
Uncertain
0.35
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.76
MutPred
0.74
Gain of disorder (P = 0.0499);.;Gain of disorder (P = 0.0499);
MVP
0.70
MPC
0.21
ClinPred
0.88
D
GERP RS
6.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.76
gMVP
0.50

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: rs199811648; hg19: chr8-97269213; API