Variant 22-30426831-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 ENST00000266263.10(MTFP1):c.182A>G(p.Lys61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,611,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

MTFP1
ENST00000266263.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

Variant links:

Genes affected

MTFP1 (HGNC:26945): (mitochondrial fission process 1) MTP18 is a mitochondrial protein and downstream target of the phosphatidylinositol 3-kinase (see PIK3CA, MIM 171834) signaling pathway that plays a role in cell viability and mitochondrial dynamics (Tondera et al., 2004 [PubMed 15155745]).[supplied by OMIM, Mar 2008]

MTFP1 links:

ENSG00000249590 (HGNC:):

ENSG00000249590 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=0.12457904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTFP1	NM_016498.5 linkuse as main transcript	c.182A>G	p.Lys61Arg	missense_variant	2/4	ENST00000266263.10	NP_057582.2	Q9UDX5-1A0A024R1E4
MTFP1	NM_001003704.3 linkuse as main transcript	c.182A>G	p.Lys61Arg	missense_variant	2/3		NP_001003704.1	Q9UDX5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTFP1	ENST00000266263.10 linkuse as main transcript	c.182A>G	p.Lys61Arg	missense_variant	2/4	1	NM_016498.5	ENSP00000266263.5		Q9UDX5-1
ENSG00000249590	ENST00000439838.5 linkuse as main transcript	c.698A>G	p.Lys233Arg	missense_variant	7/9	2		ENSP00000415178.1		H7C417

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249282

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134928

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1459154

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Apr 12, 2022

The c.182A>G (p.K61R) alteration is located in exon 2 (coding exon 2) of the MTFP1 gene. This alteration results from a A to G substitution at nucleotide position 182, causing the lysine (K) at amino acid position 61 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

0.058

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

.;T;T;.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.031

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.76

T;T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.33

.;N;.;N;.

MutationTaster

Benign

0.91

D;D;D

PROVEAN

Benign

-0.66

N;N;.;N;N

REVEL

Benign

0.042

Sift

Benign

0.15

T;T;.;T;T

Sift4G

Benign

0.78

T;T;T;T;T

Polyphen

0.0, 0.36

.;B;.;B;.

Vest4

0.27, 0.26, 0.30, 0.27

MutPred

0.45

.;Loss of methylation at K61 (P = 0.0185);Loss of methylation at K61 (P = 0.0185);Loss of methylation at K61 (P = 0.0185);Loss of methylation at K61 (P = 0.0185);

MVP

0.31

MPC

0.23

ClinPred

0.14

GERP RS

4.4

Varity_R

0.11

gMVP

0.58

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