Variant 8-96256985-G-C details in Genebe, Genetics Data Aggregator

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

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]

MTERF3 links:

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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	Protein
MTERF3	NM_015942.5 linkuse as main transcript	c.464C>G	p.Thr155Ser	missense_variant	3/8	ENST00000287025.4	NP_057026.3
MTERF3	NM_001286643.1 linkuse as main transcript	c.464C>G	p.Thr155Ser	missense_variant	3/9		NP_001273572.1
MTERF3	XM_011517054.3 linkuse as main transcript	c.125C>G	p.Thr42Ser	missense_variant	3/8		XP_011515356.1
MTERF3	NM_001362964.1 linkuse as main transcript	c.-107C>G		5_prime_UTR_variant	3/8		NP_001349893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTERF3	ENST00000287025.4 linkuse as main transcript	c.464C>G	p.Thr155Ser	missense_variant	3/8	1	NM_015942.5	ENSP00000287025	P1	Q96E29-1
MTERF3	ENST00000523821.5 linkuse as main transcript	c.464C>G	p.Thr155Ser	missense_variant	3/9	1		ENSP00000429400
MTERF3	ENST00000522822.5 linkuse as main transcript	c.101C>G	p.Thr34Ser	missense_variant	1/6	2		ENSP00000430138		Q96E29-3
MTERF3	ENST00000524341.5 linkuse as main transcript	c.-107C>G		5_prime_UTR_variant	1/5	3		ENSP00000429267

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152192

Hom.:

Cov.:

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:

AN:

249958

Hom.:

AF XY:

0.0000370

AC XY:

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.:

Cov.:

AF XY:

0.0000606

AC XY:

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:

AN:

152310

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

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.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000412

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The 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

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

.;.;T

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.94

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.0097

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.60

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over