Variant chr2-227325204-C-T 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 ENST00000423098.5(MFF):c.-430C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 147,896 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 139 hom., cov: 35)

Exomes 𝑓: 0.079 ( 0 hom. )

Consequence

MFF
ENST00000423098.5 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.23

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=-0.54).

BP6

Variant 2-227325204-C-T is Benign according to our data. Variant chr2-227325204-C-T is described in ClinVar as [Benign]. Clinvar id is 1294408.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 = 0.0326 (4817/147858) while in subpopulation AMR AF= 0.0453 (673/14852). AF 95% confidence interval is 0.0425. There are 139 homozygotes in gnomad4. There are 2644 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 139 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFF	NM_001277062.2 linkuse as main transcript			upstream_gene_variant		ENST00000304593.14	NP_001263991.1
MFF-DT	NR_102371.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFF	ENST00000304593.14 linkuse as main transcript			upstream_gene_variant		2	NM_001277062.2	ENSP00000304898	P1	Q9GZY8-2
MFF-DT	ENST00000439598.6 linkuse as main transcript			upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4815

AN:

147746

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00771

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.0452

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0156

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0224

Gnomad NFE

AF:

0.0365

Gnomad OTH

AF:

0.0277

GnomAD4 exome

AF:

0.0789

AC:

AN:

Hom.:

Cov.:

AF XY:

0.107

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.0714

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0326

AC:

4817

AN:

147858

Hom.:

139

Cov.:

AF XY:

0.0366

AC XY:

2644

AN XY:

72332

show subpopulations

Gnomad4 AFR

AF:

0.00769

Gnomad4 AMR

AF:

0.0453

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0154

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.0366

Gnomad4 OTH

AF:

0.0274

Alfa

AF:

0.0377

Hom.:

Bravo

AF:

0.0252

Asia WGS

AF:

0.00895

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

-0.54

CADD

Benign

DANN

Benign

0.95

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