chr3-119506235-G-C

Variant names:

• chr3-119506235-G-C
• rs1967621
• NM_016589.4:c.517+2214G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016589.4(TIMMDC1):​c.517+2214G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,218 control chromosomes in the GnomAD database, including 49,887 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 0.81 (49887 hom., cov: 33)
• Consequence: TIMMDC1 NM_016589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 31

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae)
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMMDC1	NM_016589.4	c.517+2214G>C		intron_variant	Intron 4 of 6	ENST00000494664.6	NP_057673.2
TIMMDC1	NM_001438040.1	c.194+7308G>C		intron_variant	Intron 1 of 2		NP_001424969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMMDC1	ENST00000494664.6	c.517+2214G>C		intron_variant	Intron 4 of 6	1	NM_016589.4	ENSP00000418803.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 123036 AN: 152100 Hom.: 49845 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.809 AC: 123136 AN: 152218 Hom.: 49887 Cov.: 33 AF XY: 0.811 AC XY: 60373 AN XY: 74414

African (AFR) AF: 0.823 AC: 34176 AN: 41520

American (AMR) AF: 0.773 AC: 11825 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2495 AN: 3470

East Asian (EAS) AF: 0.868 AC: 4503 AN: 5186

South Asian (SAS) AF: 0.858 AC: 4137 AN: 4824

European-Finnish (FIN) AF: 0.848 AC: 8986 AN: 10592

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54332 AN: 68014

Other (OTH) AF: 0.806 AC: 1701 AN: 2110

Alfa AF: 0.794 Hom.: 5937

Bravo AF: 0.802

Asia WGS AF: 0.846 AC: 2940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.42
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1967621; hg19: chr3-119225082;