rs4688011

Positions:

• chr3-119508400-G-A
• chr3-119508400-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016589.4(TIMMDC1):​c.517+4379G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,206 control chromosomes in the GnomAD database, including 2,339 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2339 hom., cov: 33)
• Consequence: TIMMDC1 NM_016589.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMMDC1	NM_016589.4	c.517+4379G>A		intron_variant		ENST00000494664.6	NP_057673.2
TIMMDC1	XM_017006556.2	c.195-8805G>A		intron_variant			XP_016862045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMMDC1	ENST00000494664.6	c.517+4379G>A		intron_variant		1	NM_016589.4	ENSP00000418803	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23422 AN: 152088 Hom.: 2337 Cov.: 33

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.154 AC: 23429 AN: 152206 Hom.: 2339 Cov.: 33 AF XY: 0.158 AC XY: 11782 AN XY: 74392

Gnomad4 AFR AF: 0.0355

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.167

Alfa AF: 0.175 Hom.: 1101

Bravo AF: 0.146

Asia WGS AF: 0.201 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.52

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: rs4688011; hg19: chr3-119227247;