Variant 8-96239553-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_015942.5(MTERF3):c.1192T>C(p.Phe398Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MTERF3
NM_015942.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.83

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.965

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTERF3	NM_015942.5 linkuse as main transcript	c.1192T>C	p.Phe398Leu	missense_variant	8/8	ENST00000287025.4	NP_057026.3
MTERF3	NM_001362964.1 linkuse as main transcript	c.622T>C	p.Phe208Leu	missense_variant	8/8		NP_001349893.1
MTERF3	XM_011517054.3 linkuse as main transcript	c.853T>C	p.Phe285Leu	missense_variant	8/8		XP_011515356.1
MTERF3	NM_001286643.1 linkuse as main transcript	c.*168T>C		3_prime_UTR_variant	9/9		NP_001273572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTERF3	ENST00000287025.4 linkuse as main transcript	c.1192T>C	p.Phe398Leu	missense_variant	8/8	1	NM_015942.5	ENSP00000287025	P1	Q96E29-1
MTERF3	ENST00000523821.5 linkuse as main transcript	c.*168T>C		3_prime_UTR_variant	9/9	1		ENSP00000429400
MTERF3	ENST00000522822.5 linkuse as main transcript	c.829T>C	p.Phe277Leu	missense_variant	6/6	2		ENSP00000430138		Q96E29-3
MTERF3	ENST00000524341.5 linkuse as main transcript	c.460T>C	p.Phe154Leu	missense_variant	5/5	3		ENSP00000429267

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460076

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726406

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

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

Cov.:

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 01, 2023

The c.1192T>C (p.F398L) alteration is located in exon 8 (coding exon 7) of the MTERF3 gene. This alteration results from a T to C substitution at nucleotide position 1192, causing the phenylalanine (F) at amino acid position 398 to be replaced by a leucine (L). 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

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

.;.;T

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;T;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Uncertain

0.30

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Pathogenic

0.81

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.93

MutPred

0.81

.;.;Loss of catalytic residue at A403 (P = 0.392);

MVP

0.88

MPC

0.18

ClinPred

1.0

GERP RS

5.9

Varity_R

0.93

gMVP

0.83

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over