Variant 3-119503609-G-C 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_016589.4(TIMMDC1):c.438G>C(p.Val146Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,606,236 control chromosomes in the GnomAD database, including 28,983 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2719 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26264 hom. )

Consequence

TIMMDC1
NM_016589.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.599

Variant links:

Genes affected

TIMMDC1 (HGNC:1321): (translocase of inner mitochondrial membrane domain containing 1) Located in mitochondrion and nucleoplasm. Implicated in nuclear type mitochondrial complex I deficiency 31. [provided by Alliance of Genome Resources, Apr 2022]

TIMMDC1 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=-0.49).

BP6

Variant 3-119503609-G-C is Benign according to our data. Variant chr3-119503609-G-C is described in ClinVar as [Benign]. Clinvar id is 1621743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.599 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMMDC1	NM_016589.4 link	c.438G>C	p.Val146Val	synonymous_variant	3/7	ENST00000494664.6	NP_057673.2	Q9NPL8
TIMMDC1	XM_017006556.2 link	c.194+4682G>C		intron_variant			XP_016862045.1	C9JU35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMMDC1	ENST00000494664.6 link	c.438G>C	p.Val146Val	synonymous_variant	3/7	1	NM_016589.4	ENSP00000418803.1		Q9NPL8

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28167

AN:

152084

Hom.:

2720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.177

AC:

42943

AN:

242994

Hom.:

4120

AF XY:

0.177

AC XY:

23238

AN XY:

131280

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.332

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.187

AC:

271409

AN:

1454034

Hom.:

26264

Cov.:

AF XY:

0.186

AC XY:

134458

AN XY:

723140

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.319

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.190

GnomAD4 genome

AF:

0.185

AC:

28174

AN:

152202

Hom.:

2719

Cov.:

AF XY:

0.181

AC XY:

13489

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.183

Hom.:

861

Bravo

AF:

0.186

Asia WGS

AF:

0.241

AC:

836

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

TIMMDC1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.6

DANN

Benign

0.60

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