Variant chr2-227325328-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001277062.2(MFF):c.-252C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 159,590 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 115 hom., cov: 37)

Exomes 𝑓: 0.00069 ( 0 hom. )

Consequence

MFF
NM_001277062.2 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.448

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:

MFF-DT (HGNC:41067): (MFF divergent transcript)

MFF-DT 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 (BayesDel_noAF=-0.56).

BP6

Variant 2-227325328-C-A is Benign according to our data. Variant chr2-227325328-C-A is described in ClinVar as [Benign]. Clinvar id is 1266167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0285 (4346/152326) while in subpopulation AMR AF= 0.0351 (538/15310). AF 95% confidence interval is 0.0327. There are 115 homozygotes in gnomad4. There are 2411 alleles in male gnomad4 subpopulation. Median coverage is 37. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 115 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFF	NM_001277062.2 linkuse as main transcript	c.-252C>A		5_prime_UTR_variant	1/9	ENST00000304593.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFF	ENST00000304593.14 linkuse as main transcript	c.-252C>A		5_prime_UTR_variant	1/9	2	NM_001277062.2	P1	Q9GZY8-2

Frequencies

GnomAD3 genomes

AF:

0.0285

AC:

4344

AN:

152208

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00634

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0258

GnomAD4 exome

AF:

0.000688

AC:

AN:

7264

Hom.:

Cov.:

AF XY:

0.000496

AC XY:

AN XY:

4030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00129

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0285

AC:

4346

AN:

152326

Hom.:

115

Cov.:

AF XY:

0.0324

AC XY:

2411

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00632

Gnomad4 AMR

AF:

0.0351

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0145

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.0327

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0326

Hom.:

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 22, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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