NM_012456.3:c.139G>C

Variant names:

• chr11-57528851-C-G
• rs374666302
• NM_012456.3:c.139G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012456.3(TIMM10):​c.139G>C​(p.Glu47Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TIMM10 NM_012456.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84

Genes affected

TIMM10 (HGNC:11814): (translocase of inner mitochondrial membrane 10) The mitochondrial protein encoded by this gene belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane, functioning as intermembrane space chaperones for the highly insoluble carrier proteins. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMM10	NM_012456.3	c.139G>C	p.Glu47Gln	missense_variant	Exon 3 of 3	ENST00000257245.9	NP_036588.1
TIMM10	XM_024448436.2	c.139G>C	p.Glu47Gln	missense_variant	Exon 3 of 3		XP_024304204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMM10	ENST00000257245.9	c.139G>C	p.Glu47Gln	missense_variant	Exon 3 of 3	1	NM_012456.3	ENSP00000257245.4
TIMM10	ENST00000525158.1	c.139G>C	p.Glu47Gln	missense_variant	Exon 3 of 3	2		ENSP00000433627.1
TIMM10	ENST00000525587.1	c.139G>C	p.Glu47Gln	missense_variant	Exon 3 of 3	3		ENSP00000435678.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;.;D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Uncertain	0.0011	D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.95
MVP		0.81
MPC		1.3
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.92
gMVP		0.97

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: rs374666302; hg19: chr11-57296324;