3-179378650-A-G

Position:

• chr3-179378650-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000471841.6(MFN1):​c.1498A>G​(p.Lys500Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MFN1 ENST00000471841.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60

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]

MFN1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFN1	NM_033540.3	c.1498A>G	p.Lys500Glu	missense_variant	14/18	ENST00000471841.6	NP_284941.2
MFN1	XM_005247596.5	c.1498A>G	p.Lys500Glu	missense_variant	14/18		XP_005247653.2
MFN1	XM_011512963.4	c.1057A>G	p.Lys353Glu	missense_variant	11/15		XP_011511265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFN1	ENST00000471841.6	c.1498A>G	p.Lys500Glu	missense_variant	14/18	1	NM_033540.3	ENSP00000420617.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.1498A>G (p.K500E) alteration is located in exon 14 (coding exon 13) of the MFN1 gene. This alteration results from a A to G substitution at nucleotide position 1498, causing the lysine (K) at amino acid position 500 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	20
DANN	Benign	0.76
DEOGEN2	Benign	0.18	T;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.060	N;N
REVEL	Uncertain	0.52
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.83	P;P
Vest4		0.52
MutPred		0.40		Loss of methylation at K500 (P = 0.003);Loss of methylation at K500 (P = 0.003);
MVP		0.82
MPC		0.34
ClinPred		0.75	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-179096438;