3-179348881-C-G

Position:

• chr3-179348881-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033540.3(MFN1):​c.30C>G​(p.His10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MFN1 NM_033540.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39611173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFN1	NM_033540.3	c.30C>G	p.His10Gln	missense_variant	2/18	ENST00000471841.6	NP_284941.2
MFN1	XM_005247596.5	c.30C>G	p.His10Gln	missense_variant	2/18		XP_005247653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFN1	ENST00000471841.6	c.30C>G	p.His10Gln	missense_variant	2/18	1	NM_033540.3	ENSP00000420617	P1
MFN1	ENST00000263969.9	c.30C>G	p.His10Gln	missense_variant	1/17	1		ENSP00000263969	P1
MFN1	ENST00000467174.6	c.30C>G	p.His10Gln	missense_variant	2/5	4		ENSP00000419134
MFN1	ENST00000357390.8	c.30C>G	p.His10Gln	missense_variant, NMD_transcript_variant	2/17	2		ENSP00000349963

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Jun 30, 2023

The c.30C>G (p.H10Q) alteration is located in exon 2 (coding exon 1) of the MFN1 gene. This alteration results from a C to G substitution at nucleotide position 30, causing the histidine (H) at amino acid position 10 to be replaced by a glutamine (Q). 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	0.30
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	21
DANN	Benign	0.83
DEOGEN2	Uncertain	0.58	D;T;D
Eigen	Benign	0.029
Eigen_PC	Benign	0.036
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.3	M;.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Uncertain	0.57
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.68	P;.;P
Vest4		0.52
MutPred		0.36		Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);
MVP		0.93
MPC		0.31
ClinPred		0.79	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr3-179066669;