2-227325204-C-T

Position:

• chr2-227325204-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.23

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

ACMG classification

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			upstream_gene_variant		ENST00000304593.14	NP_001263991.1
MFF-DT	NR_102371.1			upstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4815 AN: 147746 Hom.: 139 Cov.: 35

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: 3 AN: 38 Hom.: 0 Cov.: 0 AF XY: 0.107 AC XY: 3 AN XY: 28

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.: 35 AF XY: 0.0366 AC XY: 2644 AN XY: 72332

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.: 65

Bravo AF: 0.0252

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	17
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

Other links and lift over

dbSNP: rs77737296; hg19: chr2-228189920;