NM_033540.3:c.249-2013G>T

Variant names:

• chr3-179356827-G-T
• rs9822116
• NM_033540.3:c.249-2013G>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.249-2013G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,830 control chromosomes in the GnomAD database, including 21,957 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 0.52 (21957 hom., cov: 31)
• Consequence: MFN1 NM_033540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFN1	NM_033540.3	c.249-2013G>T		intron_variant	Intron 3 of 17	ENST00000471841.6	NP_284941.2
MFN1	XM_005247596.5	c.249-2013G>T		intron_variant	Intron 3 of 17		XP_005247653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFN1	ENST00000471841.6	c.249-2013G>T		intron_variant	Intron 3 of 17	1	NM_033540.3	ENSP00000420617.1
MFN1	ENST00000263969.9	c.249-2013G>T		intron_variant	Intron 2 of 16	1		ENSP00000263969.5
MFN1	ENST00000467174.6	c.249-2013G>T		intron_variant	Intron 3 of 4	4		ENSP00000419134.2
MFN1	ENST00000357390.8	n.249-2013G>T		intron_variant	Intron 3 of 16	2		ENSP00000349963.4

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78767 AN: 151712 Hom.: 21921 Cov.: 31

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.519 AC: 78847 AN: 151830 Hom.: 21957 Cov.: 31 AF XY: 0.525 AC XY: 38939 AN XY: 74190

African (AFR) AF: 0.729 AC: 30194 AN: 41402

American (AMR) AF: 0.541 AC: 8241 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1396 AN: 3466

East Asian (EAS) AF: 0.294 AC: 1511 AN: 5146

South Asian (SAS) AF: 0.484 AC: 2323 AN: 4802

European-Finnish (FIN) AF: 0.501 AC: 5273 AN: 10522

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28391 AN: 67938

Other (OTH) AF: 0.484 AC: 1022 AN: 2112

Alfa AF: 0.463 Hom.: 47173

Bravo AF: 0.529

Asia WGS AF: 0.445 AC: 1546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.18
PhyloP100		-1.3
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: rs9822116; hg19: chr3-179074615;