Variant 8-96256964-A-G 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.485T>C(p.Leu162Pro) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,598,420 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

MTERF3
NM_015942.5 missense, splice_region

Scores

Splicing: ADA: 0.7001

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.65

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
MTERF3	NM_015942.5 linkuse as main transcript	c.485T>C	p.Leu162Pro	missense_variant, splice_region_variant	3/8	ENST00000287025.4
MTERF3	NM_001286643.1 linkuse as main transcript	c.485T>C	p.Leu162Pro	missense_variant, splice_region_variant	3/9
MTERF3	XM_011517054.3 linkuse as main transcript	c.146T>C	p.Leu49Pro	missense_variant, splice_region_variant	3/8
MTERF3	NM_001362964.1 linkuse as main transcript	c.-86T>C		splice_region_variant, 5_prime_UTR_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTERF3	ENST00000287025.4 linkuse as main transcript	c.485T>C	p.Leu162Pro	missense_variant, splice_region_variant	3/8	1	NM_015942.5	P1	Q96E29-1
MTERF3	ENST00000523821.5 linkuse as main transcript	c.485T>C	p.Leu162Pro	missense_variant, splice_region_variant	3/9	1
MTERF3	ENST00000522822.5 linkuse as main transcript	c.122T>C	p.Leu41Pro	missense_variant, splice_region_variant	1/6	2			Q96E29-3
MTERF3	ENST00000524341.5 linkuse as main transcript	c.-86T>C		splice_region_variant, 5_prime_UTR_variant	1/5	3

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0000654

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:

0.000456

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000174

AC:

AN:

235292

Hom.:

AF XY:

0.000197

AC XY:

AN XY:

127072

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:

0.000376

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000269

AC:

389

AN:

1446170

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

206

AN XY:

719020

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.0000250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000334

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

AF:

0.000276

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000406

Hom.:

Bravo

AF:

0.000280

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000206

AC:

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

Dec 07, 2021

The c.485T>C (p.L162P) alteration is located in exon 3 (coding exon 2) of the MTERF3 gene. This alteration results from a T to C substitution at nucleotide position 485, causing the leucine (L) at amino acid position 162 to be replaced by a proline (P). 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

0.90

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Pathogenic

0.15

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Benign

-0.81

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-6.8

D;D;D

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.91

MVP

0.54

MPC

0.25

ClinPred

0.92

GERP RS

6.2

Varity_R

0.95

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.70

dbscSNV1_RF

Pathogenic

0.74

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