Variant 2-227329764-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001277062.2(MFF):c.-40-862A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,538,740 control chromosomes in the GnomAD database, including 93,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6830 hom., cov: 32)

Exomes 𝑓: 0.36 ( 87129 hom. )

Consequence

MFF
NM_001277062.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.48

Variant links:

Genes affected

MFF (HGNC:24858): (mitochondrial fission factor) This is a nuclear gene encoding a protein that functions in mitochondrial and peroxisomal fission. The encoded protein recruits dynamin-1-like protein (DNM1L) to mitochondria. There are multiple pseudogenes for this gene on chromosomes 1, 5, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

MFF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021739304).

BP6

Variant 2-227329764-A-T is Benign according to our data. Variant chr2-227329764-A-T is described in ClinVar as [Benign]. Clinvar id is 379993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFF	NM_001277062.2 linkuse as main transcript	c.-40-862A>T		intron_variant		ENST00000304593.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFF	ENST00000304593.14 linkuse as main transcript	c.-40-862A>T		intron_variant		2	NM_001277062.2	P1	Q9GZY8-2

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43606

AN:

151364

Hom.:

6834

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.353

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.290

GnomAD3 exomes

AF:

0.322

AC:

79139

AN:

246136

Hom.:

12693

AF XY:

0.337

AC XY:

44841

AN XY:

133054

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.225

Gnomad SAS exome

AF:

0.449

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.368

Gnomad OTH exome

AF:

0.334

GnomAD4 exome

AF:

0.356

AC:

494265

AN:

1387258

Hom.:

87129

Cov.:

AF XY:

0.361

AC XY:

249984

AN XY:

692708

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.449

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.370

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.288

AC:

43596

AN:

151482

Hom.:

6830

Cov.:

AF XY:

0.285

AC XY:

21039

AN XY:

73950

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.388

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.464

Gnomad4 FIN

AF:

0.301

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.286

Alfa

AF:

0.346

Hom.:

2725

TwinsUK

AF:

0.396

AC:

1470

ALSPAC

AF:

0.383

AC:

1477

ESP6500AA

AF:

0.118

AC:

521

ESP6500EA

AF:

0.349

AC:

3003

ExAC

AF:

0.330

AC:

40031

Asia WGS

AF:

0.297

AC:

1035

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.035

T;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.0033

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.64

T;T;T

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

0.86

P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.33

N;D;N

REVEL

Benign

0.046

Sift

Uncertain

0.0060

D;.;D

Sift4G

Benign

0.074

T;D;D

Polyphen

0.0

B;.;.

Vest4

0.058

MPC

0.26

ClinPred

0.029

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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