Variant chr19-39480654-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The ENST00000544017.5(TIMM50):c.110T>C(p.Phe37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,614,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

TIMM50
ENST00000544017.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.308

Variant links:

Genes affected

TIMM50 (HGNC:23656): (translocase of inner mitochondrial membrane 50) This gene encodes a subunit of the TIM23 inner mitochondrial membrane translocase complex. The encoded protein functions as the receptor subunit that recognizes the mitochondrial targeting signal, or presequence, on protein cargo that is destined for the mitochondrial inner membrane and matrix. This protein may also play a role in maintaining the membrane permeability barrier, and knockdown of this gene in human cells results in the release of cytochrome c and apoptosis. [provided by RefSeq, Jul 2016]

TIMM50 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.00376603).

BP6

Variant 19-39480654-T-C is Benign according to our data. Variant chr19-39480654-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1659560.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000801 (122/152348) while in subpopulation AFR AF= 0.00274 (114/41586). AF 95% confidence interval is 0.00233. There are 0 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMM50	ENST00000544017.5 linkuse as main transcript	c.110T>C	p.Phe37Ser	missense_variant	1/11	1			Q3ZCQ8-2
TIMM50	ENST00000601358.5 linkuse as main transcript	c.-200T>C		5_prime_UTR_variant, NMD_transcript_variant	1/10	1

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000956

GnomAD3 exomes

AF:

0.000263

AC:

AN:

251424

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000923

AC:

135

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00293

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000801

AC:

122

AN:

152348

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00274

Gnomad4 AMR

AF:

0.000327

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:

0.000946

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.000941

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000321

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.6

DANN

Benign

0.91

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.029

M_CAP

Benign

0.00095

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.13

N;.

REVEL

Benign

0.062

Sift

Benign

0.45

T;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0

B;B

Vest4

0.21

MVP

0.072

MPC

0.57

ClinPred

0.023

GERP RS

-7.1

gMVP

0.056

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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