NM_138358.4:c.230C>T

Variant names:

• chr19-10929149-C-T
• NM_138358.4:c.230C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138358.4(TIMM29):​c.230C>T​(p.Ala77Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TIMM29 NM_138358.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.855
• Publications: 0 publications found

Genes affected

TIMM29 (HGNC:25152): (translocase of inner mitochondrial membrane 29) Enables protein transporter activity. Involved in protein insertion into mitochondrial inner membrane. Located in mitochondrial inner membrane and mitochondrial intermembrane space. Part of TIM22 mitochondrial import inner membrane insertion complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17006505).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138358.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM29	NM_138358.4	MANE Select	c.230C>T	p.Ala77Val	missense	Exon 2 of 2	NP_612367.1	Q9BSF4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM29	ENST00000270502.7	TSL:1 MANE Select	c.230C>T	p.Ala77Val	missense	Exon 2 of 2	ENSP00000270502.5	Q9BSF4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1301832 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 637228

African (AFR) AF: 0.00 AC: 0 AN: 26344

American (AMR) AF: 0.00 AC: 0 AN: 21768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19700

East Asian (EAS) AF: 0.00 AC: 0 AN: 32418

South Asian (SAS) AF: 0.00 AC: 0 AN: 65902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1046552

Other (OTH) AF: 0.00 AC: 0 AN: 54138

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.85
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.18
Sift	Benign	0.22	T
Sift4G	Benign	0.14	T
Polyphen		0.47	P
Vest4		0.22
MutPred		0.63		Loss of disorder (P = 0.0579)
MVP		0.040
MPC		1.0
ClinPred		0.16	T
GERP RS		2.3
PromoterAI		-0.0016	Neutral
Varity_R		0.059
gMVP		0.38
Mutation Taster		=88/12	polymorphism

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

hg19: chr19-11039825;