rs3976523

chr3-179381391-C-Achr3-179381391-C-T

Variant summary

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

The NM_033540.3(MFN1):c.1662+2577C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,160 control chromosomes in the GnomAD database, including 38,054 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 0.70 (38054 hom., cov: 33)
• Consequence: MFN1 NM_033540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFN1	NM_033540.3	c.1662+2577C>A		intron_variant		ENST00000471841.6
MFN1	XM_005247596.5	c.1662+2577C>A		intron_variant
MFN1	XM_011512963.4	c.1221+2577C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFN1	ENST00000471841.6	c.1662+2577C>A		intron_variant		1	NM_033540.3	P1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106954 AN: 152042 Hom.: 38014 Cov.: 33

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.704 AC: 107047 AN: 152160 Hom.: 38054 Cov.: 33 AF XY: 0.706 AC XY: 52535 AN XY: 74406

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.720

Alfa AF: 0.590 Hom.: 1907

Bravo AF: 0.714

Asia WGS AF: 0.738 AC: 2564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.83
Dann	Benign	0.41

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: rs3976523; hg19: chr3-179099179; COSMIC: COSV54938660; COSMIC: COSV54938660;