ENST00000377773.9:c.179C>G

Variant names:

• chr9-37592354-G-C
• rs1208235611
• ENST00000377773.9:c.179C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000377773.9(TOMM5):​c.179C>G​(p.Pro60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P60L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TOMM5 ENST00000377773.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• Publications: 0 publications found

Genes affected

TOMM5 (HGNC:31369): (translocase of outer mitochondrial membrane 5) Predicted to be involved in protein targeting to mitochondrion. Located in mitochondrion. Part of mitochondrial outer membrane translocase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256966 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06452939).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377773.9. 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
	TOMM5	NM_001001790.3	MANE Select	c.121+58C>G		intron	N/A	NP_001001790.1	Q8N4H5-1
	TOMM5	NM_001134484.2		c.179C>G	p.Pro60Arg	missense	Exon 1 of 2	NP_001127956.1	Q8N4H5-2
	TOMM5	NM_001134485.2		c.179C>G	p.Pro60Arg	missense	Exon 1 of 2	NP_001127957.1	Q8N4H5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM5	ENST00000377773.9	TSL:1	c.179C>G	p.Pro60Arg	missense	Exon 1 of 2	ENSP00000367004.5	Q8N4H5-3
	TOMM5	ENST00000321301.7	TSL:1 MANE Select	c.121+58C>G		intron	N/A	ENSP00000313584.6	Q8N4H5-1
	ENSG00000256966	ENST00000537239.2	TSL:5	n.116C>G		non_coding_transcript_exon	Exon 1 of 3	ENSP00000457849.1	H3BUX3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459086 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725516

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00 AC: 0 AN: 85584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110728

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.0
DANN	Benign	0.88
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.97
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.015
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.089	T
Vest4		0.045
MutPred		0.31		Gain of MoRF binding (P = 0.0288)
MVP		0.068
MPC		1.1
ClinPred		0.79	D
GERP RS		-2.5
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.025
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1208235611; hg19: chr9-37592351;