2-227325269-C-A

Position:

• chr2-227325269-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277062.2(MFF):​c.-311C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,898 control chromosomes in the GnomAD database, including 1,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1076 hom., cov: 35)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: MFF NM_001277062.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.118

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=-0.98).
• BP6: Variant 2-227325269-C-A is Benign according to our data. Variant chr2-227325269-C-A is described in ClinVar as [Benign]. Clinvar id is 1292201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFF	NM_001277062.2	c.-311C>A		5_prime_UTR_variant	1/9	ENST00000304593.14	NP_001263991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFF	ENST00000304593.14	c.-311C>A		5_prime_UTR_variant	1/9	2	NM_001277062.2	ENSP00000304898	P1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17436 AN: 152160 Hom.: 1074 Cov.: 35

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.0113 AC: 7 AN: 620 Hom.: 0 Cov.: 0 AF XY: 0.0148 AC XY: 5 AN XY: 338

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.0140

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.115 AC: 17456 AN: 152278 Hom.: 1076 Cov.: 35 AF XY: 0.113 AC XY: 8422 AN XY: 74450

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.0940

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0710

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0737 Hom.: 112

Asia WGS AF: 0.0780 AC: 274 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	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	9.6
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs28365988; hg19: chr2-228189985;