2-227325534-GC-G

Position:

• chr2-227325534-GC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001277062.2(MFF):​c.-153+114del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 151,850 control chromosomes in the GnomAD database, including 1,398 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1397 hom., cov: 30)
  • Exomes 𝑓: 0.091 (1 hom.)
• Consequence: MFF NM_001277062.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.550

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 -10 ACMG points.

• BP6: Variant 2-227325534-GC-G is Benign according to our data. Variant chr2-227325534-GC-G is described in ClinVar as [Benign]. Clinvar id is 1257414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFF	NM_001277062.2	c.-153+114del		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+114del		intron_variant		2	NM_001277062.2	ENSP00000304898	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20139 AN: 151602 Hom.: 1393 Cov.: 30

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.0909 AC: 12 AN: 132 Hom.: 1 Cov.: 0 AF XY: 0.0729 AC XY: 7 AN XY: 96

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0965

GnomAD4 genome AF: 0.133 AC: 20164 AN: 151718 Hom.: 1397 Cov.: 30 AF XY: 0.131 AC XY: 9722 AN XY: 74166

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0718

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0662 Hom.: 76

Bravo AF: 0.131

Asia WGS AF: 0.0810 AC: 284 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs145855603; hg19: chr2-228190250;