chr2-227325651-T-C

Position:

• chr2-227325651-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277062.2(MFF):​c.-153+224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.957 in 152,346 control chromosomes in the GnomAD database, including 69,968 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.96 (69940 hom., cov: 32)
  • Exomes 𝑓: 0.98 (28 hom.)
• Consequence: MFF NM_001277062.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFF	NM_001277062.2	c.-153+224T>C		intron_variant		ENST00000304593.14	NP_001263991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFF	ENST00000304593.14	c.-153+224T>C		intron_variant		2	NM_001277062.2	ENSP00000304898.10

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145624 AN: 152170 Hom.: 69910 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 0.972

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.967

GnomAD4 exome AF: 0.983 AC: 57 AN: 58 Hom.: 28 Cov.: 0 AF XY: 0.977 AC XY: 43 AN XY: 44

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.957 AC: 145703 AN: 152288 Hom.: 69940 Cov.: 32 AF XY: 0.957 AC XY: 71281 AN XY: 74460

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.979

Gnomad4 ASJ AF: 0.972

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.960

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.993

Gnomad4 OTH AF: 0.967

Alfa AF: 0.973 Hom.: 8956

Bravo AF: 0.953

Asia WGS AF: 0.968 AC: 3365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10176715; hg19: chr2-228190367;