3-119498746-C-T

Variant names:

• chr3-119498746-C-T
• rs2081843337
• NM_016589.4:c.13C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016589.4(TIMMDC1):​c.13C>T​(p.Pro5Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TIMMDC1 NM_016589.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3979441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMMDC1	NM_016589.4	c.13C>T	p.Pro5Ser	missense_variant	Exon 1 of 7	ENST00000494664.6	NP_057673.2
TIMMDC1	XM_017006556.2	c.13C>T	p.Pro5Ser	missense_variant	Exon 1 of 3		XP_016862045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMMDC1	ENST00000494664.6	c.13C>T	p.Pro5Ser	missense_variant	Exon 1 of 7	1	NM_016589.4	ENSP00000418803.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0015	T;T;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.017	D;D;D
Sift4G	Uncertain	0.055	T;D;T
Polyphen		0.96	D;.;.
Vest4		0.35
MutPred		0.43		Loss of glycosylation at P5 (P = 0.0048);Loss of glycosylation at P5 (P = 0.0048);Loss of glycosylation at P5 (P = 0.0048);
MVP		0.40
MPC		0.34
ClinPred		0.96	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.15
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2081843337; hg19: chr3-119217593;