2-227356053-T-G

Variant names:

• chr2-227356053-T-G
• rs7560053
• NM_001277062.2:c.744+292T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001277062.2(MFF):​c.744+292T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MFF NM_001277062.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 23 publications found

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 Gene-Disease associations (from GenCC):

• encephalopathy due to defective mitochondrial and peroxisomal fission 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• encephalopathy due to mitochondrial and peroxisomal fission defect

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277062.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFF	NM_001277062.2	MANE Select	c.744+292T>G		intron	N/A	NP_001263991.1	Q9GZY8-2
	MFF	NM_001277061.2		c.897+292T>G		intron	N/A	NP_001263990.1	Q9GZY8-1
	MFF	NM_020194.5		c.897+292T>G		intron	N/A	NP_064579.3	Q9GZY8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFF	ENST00000304593.14	TSL:2 MANE Select	c.744+292T>G		intron	N/A	ENSP00000304898.10	Q9GZY8-2
	MFF	ENST00000337110.11	TSL:1	c.600+292T>G		intron	N/A	ENSP00000338412.7	Q9GZY8-3
	MFF	ENST00000353339.8	TSL:5	c.897+292T>G		intron	N/A	ENSP00000302037.4	Q9GZY8-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		-0.038

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

Other links and lift over

dbSNP: rs7560053; hg19: chr2-228220769;