Variant 19-7927241-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006351.4(TIMM44):c.1305C>T(p.Tyr435Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,612,356 control chromosomes in the GnomAD database, including 4,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 475 hom., cov: 32)

Exomes 𝑓: 0.070 ( 3659 hom. )

Consequence

TIMM44
NM_006351.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0200

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 19-7927241-G-A is Benign according to our data. Variant chr19-7927241-G-A is described in ClinVar as [Benign]. Clinvar id is 137649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM44	NM_006351.4 link	c.1305C>T	p.Tyr435Tyr	synonymous_variant	13/13	ENST00000270538.8	NP_006342.2	O43615

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMM44	ENST00000270538.8 link	c.1305C>T	p.Tyr435Tyr	synonymous_variant	13/13	1	NM_006351.4	ENSP00000270538.2		O43615

Frequencies

GnomAD3 genomes

AF:

0.0771

AC:

11736

AN:

152124

Hom.:

474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0584

Gnomad ASJ

AF:

0.0732

Gnomad EAS

AF:

0.0428

Gnomad SAS

AF:

0.0472

Gnomad FIN

AF:

0.0663

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0717

Gnomad OTH

AF:

0.0761

GnomAD3 exomes

AF:

0.0624

AC:

15441

AN:

247580

Hom.:

498

AF XY:

0.0619

AC XY:

8323

AN XY:

134474

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.0365

Gnomad ASJ exome

AF:

0.0706

Gnomad EAS exome

AF:

0.0370

Gnomad SAS exome

AF:

0.0538

Gnomad FIN exome

AF:

0.0718

Gnomad NFE exome

AF:

0.0684

Gnomad OTH exome

AF:

0.0625

GnomAD4 exome

AF:

0.0696

AC:

101574

AN:

1460114

Hom.:

3659

Cov.:

AF XY:

0.0690

AC XY:

50130

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.0379

Gnomad4 ASJ exome

AF:

0.0706

Gnomad4 EAS exome

AF:

0.0486

Gnomad4 SAS exome

AF:

0.0560

Gnomad4 FIN exome

AF:

0.0704

Gnomad4 NFE exome

AF:

0.0716

Gnomad4 OTH exome

AF:

0.0691

GnomAD4 genome

AF:

0.0771

AC:

11745

AN:

152242

Hom.:

475

Cov.:

AF XY:

0.0762

AC XY:

5673

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0584

Gnomad4 ASJ

AF:

0.0732

Gnomad4 EAS

AF:

0.0429

Gnomad4 SAS

AF:

0.0471

Gnomad4 FIN

AF:

0.0663

Gnomad4 NFE

AF:

0.0717

Gnomad4 OTH

AF:

0.0753

Alfa

AF:

0.0725

Hom.:

188

Bravo

AF:

0.0750

Asia WGS

AF:

0.0490

AC:

172

AN:

3478

EpiCase

AF:

0.0720

EpiControl

AF:

0.0710

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 23, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.9

DANN

Benign

0.95

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