rs1131265

chr3-119503609-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016589.4(TIMMDC1):c.438G>C(p.Val146=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.599

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]

ACMG classification

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	UniProt
TIMMDC1	NM_016589.4	c.438G>C	p.Val146=	synonymous_variant	3/7	ENST00000494664.6
TIMMDC1	XM_017006556.2	c.194+4682G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMMDC1	ENST00000494664.6	c.438G>C	p.Val146=	synonymous_variant	3/7	1	NM_016589.4	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28167 AN: 152084 Hom.: 2720 Cov.: 32

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

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.: 30 AF XY: 0.186 AC XY: 134458 AN XY: 723140

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.: 32 AF XY: 0.181 AC XY: 13489 AN XY: 74412

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

TIMMDC1-related disorder Benign:1

Benign, criteria provided, single submitter

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

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

Other links and lift over

dbSNP: rs1131265; hg19: chr3-119222456; COSMIC: COSV51786217;