rs369567784

Variant names:

• chr19-44891528-C-G
• rs369567784
• NM_001128917.2:c.113C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-44891528-C-G
• chr19-44891528-C-T

Variant summary

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

The NM_001128917.2(TOMM40):​c.113C>G​(p.Pro38Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000795 in 1,257,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P38L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: TOMM40 NM_001128917.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.13
• Publications: 0 publications found

Genes affected

TOMM40 (HGNC:18001): (translocase of outer mitochondrial membrane 40) The protein encoded by this gene is localized in the outer membrane of the mitochondria. It is the channel-forming subunit of the translocase of the mitochondrial outer membrane (TOM) complex that is essential for import of protein precursors into mitochondria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128917.2. 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
	TOMM40	NM_001128917.2	MANE Select	c.113C>G	p.Pro38Arg	missense	Exon 1 of 9	NP_001122389.1	O96008-1
	TOMM40	NM_001128916.2		c.113C>G	p.Pro38Arg	missense	Exon 2 of 10	NP_001122388.1	O96008-1
	TOMM40	NM_006114.3		c.113C>G	p.Pro38Arg	missense	Exon 2 of 10	NP_006105.1	O96008-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	ENST00000426677.7	TSL:1 MANE Select	c.113C>G	p.Pro38Arg	missense	Exon 1 of 9	ENSP00000410339.1	O96008-1
	TOMM40	ENST00000252487.9	TSL:1	c.113C>G	p.Pro38Arg	missense	Exon 2 of 10	ENSP00000252487.4	O96008-1
	TOMM40	ENST00000405636.6	TSL:1	c.113C>G	p.Pro38Arg	missense	Exon 2 of 10	ENSP00000385184.2	O96008-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.95e-7 AC: 1 AN: 1257270 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 616182

African (AFR) AF: 0.00 AC: 0 AN: 25776

American (AMR) AF: 0.00 AC: 0 AN: 21292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21238

East Asian (EAS) AF: 0.00 AC: 0 AN: 27434

South Asian (SAS) AF: 0.00 AC: 0 AN: 63852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31446

Middle Eastern (MID) AF: 0.000275 AC: 1 AN: 3632

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1011268

Other (OTH) AF: 0.00 AC: 0 AN: 51332

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.1
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.070	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.32		Gain of sheet (P = 0.0149)
MVP		0.26
MPC		2.0
ClinPred		0.91	D
GERP RS		4.4
PromoterAI		0.0015	Neutral
Varity_R		0.32
Mutation Taster		=39/61	disease causing

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

dbSNP: rs369567784; hg19: chr19-45394785;