NM_016589.4:c.175C>G

Variant names:

• chr3-119498908-C-G
• rs774619141
• NM_016589.4:c.175C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016589.4(TIMMDC1):​c.175C>G​(p.Arg59Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TIMMDC1 NM_016589.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21445054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMMDC1	NM_016589.4	c.175C>G	p.Arg59Gly	missense_variant	Exon 1 of 7	ENST00000494664.6	NP_057673.2
TIMMDC1	XM_017006556.2	c.175C>G	p.Arg59Gly	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.175C>G	p.Arg59Gly	missense_variant	Exon 1 of 7	1	NM_016589.4	ENSP00000418803.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250974 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135842

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461800 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.9	D;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D;D;T
Sift4G	Uncertain	0.016	D;T;D
Polyphen		0.32	B;.;.
Vest4		0.57
MutPred		0.35		Loss of glycosylation at K64 (P = 0.0722);Loss of glycosylation at K64 (P = 0.0722);Loss of glycosylation at K64 (P = 0.0722);
MVP		0.35
MPC		0.37
ClinPred		0.89	D
GERP RS		4.0
Varity_R		0.24
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs774619141; hg19: chr3-119217755;