Variant 22-30428462-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_016498.5(MTFP1):c.429G>A(p.Arg143=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000248 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MTFP1
NM_016498.5 splice_region, synonymous

Scores

Splicing: ADA: 0.9940

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.77

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24273783).

BP6

Variant 22-30428462-G-A is Benign according to our data. Variant chr22-30428462-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3296605.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTFP1	NM_016498.5 linkuse as main transcript	c.429G>A	p.Arg143=	splice_region_variant, synonymous_variant	4/4	ENST00000266263.10	NP_057582.2
MTFP1	NM_001003704.3 linkuse as main transcript	c.196G>A	p.Val66Ile	missense_variant, splice_region_variant	3/3		NP_001003704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTFP1	ENST00000266263.10 linkuse as main transcript	c.429G>A	p.Arg143=	splice_region_variant, synonymous_variant	4/4	1	NM_016498.5	ENSP00000266263	P1	Q9UDX5-1
MTFP1	ENST00000355143.8 linkuse as main transcript	c.196G>A	p.Val66Ile	missense_variant, splice_region_variant	3/3	2		ENSP00000347267		Q9UDX5-2
MTFP1	ENST00000407550.3 linkuse as main transcript	c.360G>A	p.Arg120=	splice_region_variant, synonymous_variant	4/4	2		ENSP00000383926
MTFP1	ENST00000412752.5 linkuse as main transcript	c.*253G>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	4/4	3		ENSP00000393954

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250538

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135464

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461784

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727200

show subpopulations

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:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000709

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

1.0

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.28

M_CAP

Benign

0.054

MetaRNN

Benign

0.24

MetaSVM

Uncertain

-0.19

MutationTaster

Benign

0.97

D;D;D

PROVEAN

Benign

-0.21

REVEL

Uncertain

0.31

Sift

Benign

0.046

Sift4G

Benign

0.44

Polyphen

1.0

Vest4

0.10

MVP

0.41

ClinPred

0.38

GERP RS

5.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Benign

0.68

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