rs13098637

Positions:

• chr3-179375026-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033540.3(MFN1):​c.976-194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,328 control chromosomes in the GnomAD database, including 1,167 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 0.11 (1167 hom., cov: 32)
• Consequence: MFN1 NM_033540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715

Genes affected

MFN1 (HGNC:18262): (mitofusin 1) The protein encoded by this gene is a mediator of mitochondrial fusion. This protein and mitofusin 2 are homologs of the Drosophila protein fuzzy onion (Fzo). They are mitochondrial membrane proteins that interact with each other to facilitate mitochondrial targeting. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFN1	NM_033540.3	c.976-194T>C		intron_variant		ENST00000471841.6
MFN1	XM_005247596.5	c.976-194T>C		intron_variant
MFN1	XM_011512963.4	c.535-194T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFN1	ENST00000471841.6	c.976-194T>C		intron_variant		1	NM_033540.3	P1
MFN1	ENST00000263969.9	c.976-194T>C		intron_variant		1		P1
MFN1	ENST00000474903.1	c.565-194T>C		intron_variant		1
MFN1	ENST00000357390.8	c.976-194T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16763 AN: 152210 Hom.: 1167 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0995

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0711

Gnomad SAS AF: 0.0781

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.110 AC: 16763 AN: 152328 Hom.: 1167 Cov.: 32 AF XY: 0.107 AC XY: 7937 AN XY: 74494

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.0993

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.0712

Gnomad4 SAS AF: 0.0785

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.123

Alfa AF: 0.140 Hom.: 380

Bravo AF: 0.108

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.86

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: rs13098637; hg19: chr3-179092814;