chr2-227325651-T-C

Variant names:

• chr2-227325651-T-C
• rs10176715
• NM_001277062.2:c.-153+224T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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-DT (HGNC:41067): (MFF divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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.

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.-153+224T>C		intron	N/A	NP_001263991.1
	MFF	NM_001277061.2		c.-253+224T>C		intron	N/A	NP_001263990.1
	MFF	NM_001277063.2		c.-153+224T>C		intron	N/A	NP_001263992.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFF	ENST00000304593.14	TSL:2 MANE Select	c.-153+224T>C		intron	N/A	ENSP00000304898.10
	MFF	ENST00000337110.11	TSL:1	c.-153+224T>C		intron	N/A	ENSP00000338412.7
	MFF	ENST00000868634.1		c.-670T>C		5_prime_UTR	Exon 1 of 10	ENSP00000538693.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 1.00 AC: 4 AN: 4

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 46 AN: 46

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.870 AC: 36150 AN: 41542

American (AMR) AF: 0.979 AC: 14999 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 3374 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5155 AN: 5160

South Asian (SAS) AF: 0.960 AC: 4637 AN: 4830

European-Finnish (FIN) AF: 0.999 AC: 10598 AN: 10612

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67556 AN: 68040

Other (OTH) AF: 0.967 AC: 2043 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.70
PhyloP100		-0.50
PromoterAI		-0.053	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10176715; hg19: chr2-228190367;