chr2-227325435-T-C

Position:

• chr2-227325435-T-C

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.-153+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 152,470 control chromosomes in the GnomAD database, including 70,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (69899 hom., cov: 31)
  • Exomes 𝑓: 0.99 (204 hom.)
• Consequence: MFF NM_001277062.2 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.182

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=-0.87).
• BP6: Variant 2-227325435-T-C is Benign according to our data. Variant chr2-227325435-T-C is described in ClinVar as [Benign]. Clinvar id is 1294402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	UniProt
MFF	NM_001277062.2	c.-153+8T>C		splice_region_variant, intron_variant		ENST00000304593.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFF	ENST00000304593.14	c.-153+8T>C		splice_region_variant, intron_variant		2	NM_001277062.2	P1

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145535 AN: 151946 Hom.: 69869 Cov.: 31

Gnomad AFR AF: 0.874

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: 0.993 AC: 411 AN: 414 Hom.: 204 Cov.: 0 AF XY: 0.994 AC XY: 308 AN XY: 310

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.997

Gnomad4 OTH exome AF: 0.929

GnomAD4 genome AF: 0.958 AC: 145614 AN: 152056 Hom.: 69899 Cov.: 31 AF XY: 0.958 AC XY: 71211 AN XY: 74320

Gnomad4 AFR AF: 0.873

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: 0.967 AC: 3359 AN: 3474

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 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7576719; hg19: chr2-228190151;