Variant chr3-179368072-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033540.3(MFN1):c.944A>G(p.Gln315Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000668 in 1,574,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 0 hom. )

Consequence

MFN1
NM_033540.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10762009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFN1	NM_033540.3 linkuse as main transcript	c.944A>G	p.Gln315Arg	missense_variant	9/18	ENST00000471841.6	NP_284941.2	Q8IWA4-1
MFN1	XM_005247596.5 linkuse as main transcript	c.944A>G	p.Gln315Arg	missense_variant	9/18		XP_005247653.2	Q8IWA4-1
MFN1	XM_011512963.4 linkuse as main transcript	c.503A>G	p.Gln168Arg	missense_variant	6/15		XP_011511265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MFN1	ENST00000471841.6 linkuse as main transcript	c.944A>G	p.Gln315Arg	missense_variant	9/18	1	NM_033540.3	ENSP00000420617.1	Q8IWA4-1
MFN1	ENST00000263969.9 linkuse as main transcript	c.944A>G	p.Gln315Arg	missense_variant	8/17	1		ENSP00000263969.5	Q8IWA4-1
MFN1	ENST00000474903.1 linkuse as main transcript	c.533A>G	p.Gln178Arg	missense_variant	5/12	1		ENSP00000419926.1	H7C5H5
MFN1	ENST00000357390.8 linkuse as main transcript	n.944A>G		non_coding_transcript_exon_variant	9/17	2		ENSP00000349963.4	Q8IWA4-2

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000868

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000238

AC:

AN:

230634

Hom.:

AF XY:

0.000239

AC XY:

AN XY:

125506

show subpopulations

Gnomad AFR exome

AF:

0.0000704

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000465

Gnomad OTH exome

AF:

0.000371

GnomAD4 exome

AF:

0.000693

AC:

986

AN:

1422642

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

469

AN XY:

707642

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

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:

0.000192

Gnomad4 NFE exome

AF:

0.000872

Gnomad4 OTH exome

AF:

0.000343

GnomAD4 genome

AF:

0.000434

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.000868

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000198

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.944A>G (p.Q315R) alteration is located in exon 9 (coding exon 8) of the MFN1 gene. This alteration results from a A to G substitution at nucleotide position 944, causing the glutamine (Q) at amino acid position 315 to be replaced by an arginine (R). 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

0.065

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

T;T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

.;T;D

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Uncertain

-0.016

MutationAssessor

Benign

0.11

N;N;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.80

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.15

MVP

0.85

MPC

0.19

ClinPred

0.024

GERP RS

4.2

Varity_R

0.071

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over