Variant chr19-7927167-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006351.4(TIMM44):c.*20T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 1,600,524 control chromosomes in the GnomAD database, including 4,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 462 hom., cov: 33)

Exomes 𝑓: 0.070 ( 3604 hom. )

Consequence

TIMM44
NM_006351.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.864

Variant links:

Genes affected

TIMM44 (HGNC:17316): (translocase of inner mitochondrial membrane 44) This gene encodes a peripheral membrane protein associated with the mitochondrial inner membrane translocase, which functions in the import of proteins across the mitochondrial inner membrane and into the mitochondrial matrix. The encoded protein mediates binding of mitochondrial heat shock protein 70 to the translocase of inner mitochondrial membrane 23 (TIM23) complex. Expression of this gene is upregulated in kidney in a mouse model of diabetes. A mutation in this gene is associated with familial oncocytic thyroid carcinoma. [provided by RefSeq, Jul 2016]

TIMM44 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-7927167-A-C is Benign according to our data. Variant chr19-7927167-A-C is described in ClinVar as [Benign]. Clinvar id is 137650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM44	NM_006351.4 link	c.*20T>G		3_prime_UTR_variant	13/13	ENST00000270538.8	NP_006342.2	O43615

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMM44	ENST00000270538 link	c.*20T>G		3_prime_UTR_variant	13/13	1	NM_006351.4	ENSP00000270538.2		O43615

Frequencies

GnomAD3 genomes

AF:

0.0765

AC:

11643

AN:

152138

Hom.:

461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0584

Gnomad ASJ

AF:

0.0732

Gnomad EAS

AF:

0.0432

Gnomad SAS

AF:

0.0482

Gnomad FIN

AF:

0.0664

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0716

Gnomad OTH

AF:

0.0756

GnomAD3 exomes

AF:

0.0610

AC:

14070

AN:

230638

Hom.:

426

AF XY:

0.0608

AC XY:

7690

AN XY:

126464

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.0361

Gnomad ASJ exome

AF:

0.0710

Gnomad EAS exome

AF:

0.0362

Gnomad SAS exome

AF:

0.0539

Gnomad FIN exome

AF:

0.0695

Gnomad NFE exome

AF:

0.0674

Gnomad OTH exome

AF:

0.0609

GnomAD4 exome

AF:

0.0695

AC:

100680

AN:

1448268

Hom.:

3604

Cov.:

AF XY:

0.0690

AC XY:

49691

AN XY:

720612

show subpopulations

Gnomad4 AFR exome

AF:

0.0997

Gnomad4 AMR exome

AF:

0.0376

Gnomad4 ASJ exome

AF:

0.0706

Gnomad4 EAS exome

AF:

0.0485

Gnomad4 SAS exome

AF:

0.0565

Gnomad4 FIN exome

AF:

0.0698

Gnomad4 NFE exome

AF:

0.0716

Gnomad4 OTH exome

AF:

0.0691

GnomAD4 genome

AF:

0.0765

AC:

11652

AN:

152256

Hom.:

462

Cov.:

AF XY:

0.0756

AC XY:

5631

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0584

Gnomad4 ASJ

AF:

0.0732

Gnomad4 EAS

AF:

0.0433

Gnomad4 SAS

AF:

0.0481

Gnomad4 FIN

AF:

0.0664

Gnomad4 NFE

AF:

0.0716

Gnomad4 OTH

AF:

0.0748

Alfa

AF:

0.0727

Hom.:

133

Bravo

AF:

0.0742

Asia WGS

AF:

0.0490

AC:

171

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 09, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.4

DANN

Benign

0.67

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