rs757306285

Variant names:

• chr3-179375310-G-A
• NM_033540.3:c.1066G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-179375310-G-A
• chr3-179375310-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_033540.3(MFN1):​c.1066G>A​(p.Asp356Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MFN1 NM_033540.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFN1	NM_033540.3	c.1066G>A	p.Asp356Asn	missense_variant	Exon 10 of 18	ENST00000471841.6	NP_284941.2
MFN1	XM_005247596.5	c.1066G>A	p.Asp356Asn	missense_variant	Exon 10 of 18		XP_005247653.2
MFN1	XM_011512963.4	c.625G>A	p.Asp209Asn	missense_variant	Exon 7 of 15		XP_011511265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFN1	ENST00000471841.6	c.1066G>A	p.Asp356Asn	missense_variant	Exon 10 of 18	1	NM_033540.3	ENSP00000420617.1
MFN1	ENST00000263969.9	c.1066G>A	p.Asp356Asn	missense_variant	Exon 9 of 17	1		ENSP00000263969.5
MFN1	ENST00000474903.1	c.655G>A	p.Asp219Asn	missense_variant	Exon 6 of 12	1		ENSP00000419926.1
MFN1	ENST00000357390.8	n.1066G>A		non_coding_transcript_exon_variant	Exon 10 of 17	2		ENSP00000349963.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461292 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726948

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D;D;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.10	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.84
MutPred		0.44		Gain of sheet (P = 0.0011);Gain of sheet (P = 0.0011);.;
MVP		0.98
MPC		0.70
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.80
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-179093098;