rs3976523

Variant names:

• chr3-179381391-C-A
• rs3976523
• NM_033540.3:c.1662+2577C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-179381391-C-A
• chr3-179381391-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MFN1	NM_033540.3	c.1662+2577C>A		intron_variant	Intron 14 of 17	ENST00000471841.6	NP_284941.2
MFN1	XM_005247596.5	c.1662+2577C>A		intron_variant	Intron 14 of 17		XP_005247653.2
MFN1	XM_011512963.4	c.1221+2577C>A		intron_variant	Intron 11 of 14		XP_011511265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFN1	ENST00000471841.6	c.1662+2577C>A		intron_variant	Intron 14 of 17	1	NM_033540.3	ENSP00000420617.1

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

African (AFR) AF: 0.787 AC: 32675 AN: 41502

American (AMR) AF: 0.772 AC: 11803 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2399 AN: 3470

East Asian (EAS) AF: 0.654 AC: 3388 AN: 5180

South Asian (SAS) AF: 0.720 AC: 3469 AN: 4820

European-Finnish (FIN) AF: 0.668 AC: 7073 AN: 10584

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43941 AN: 67990

Other (OTH) AF: 0.720 AC: 1520 AN: 2110

Alfa AF: 0.605 Hom.: 2147

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
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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