rs13098637

Variant names:

• chr3-179375026-T-C
• rs13098637
• NM_033540.3:c.976-194T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.58).
• 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 rank	MANE	Protein	UniProt
MFN1	NM_033540.3	c.976-194T>C		intron_variant	Intron 9 of 17	ENST00000471841.6	NP_284941.2
MFN1	XM_005247596.5	c.976-194T>C		intron_variant	Intron 9 of 17		XP_005247653.2
MFN1	XM_011512963.4	c.535-194T>C		intron_variant	Intron 6 of 14		XP_011511265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFN1	ENST00000471841.6	c.976-194T>C		intron_variant	Intron 9 of 17	1	NM_033540.3	ENSP00000420617.1
MFN1	ENST00000263969.9	c.976-194T>C		intron_variant	Intron 8 of 16	1		ENSP00000263969.5
MFN1	ENST00000474903.1	c.565-194T>C		intron_variant	Intron 5 of 11	1		ENSP00000419926.1
MFN1	ENST00000357390.8	n.976-194T>C		intron_variant	Intron 9 of 16	2		ENSP00000349963.4

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

African (AFR) AF: 0.0360 AC: 1496 AN: 41592

American (AMR) AF: 0.0993 AC: 1519 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 551 AN: 3468

East Asian (EAS) AF: 0.0712 AC: 370 AN: 5194

South Asian (SAS) AF: 0.0785 AC: 379 AN: 4826

European-Finnish (FIN) AF: 0.105 AC: 1119 AN: 10616

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10915 AN: 68016

Other (OTH) AF: 0.123 AC: 261 AN: 2114

Alfa AF: 0.133 Hom.: 398

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
PhyloP100		0.71
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: rs13098637; hg19: chr3-179092814;