rs775394719

Variant names:

• chr19-44891587-C-A
• rs775394719
• NM_001128917.2:c.172C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-44891587-C-A
• chr19-44891587-C-T

Variant summary

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

The NM_001128917.2(TOMM40):​c.172C>A​(p.Pro58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000762 in 1,313,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: TOMM40 NM_001128917.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

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

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=0.06924501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.172C>A	p.Pro58Thr	missense_variant	Exon 1 of 9	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.172C>A	p.Pro58Thr	missense_variant	Exon 1 of 9	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1313056 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 646576

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: 0.00

Gnomad4 NFE exome AF: 9.58e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000142 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.73	T;.;T;.;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.069	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N;N;N;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.4	N;N;.;N;.
REVEL	Benign	0.028
Sift	Benign	0.12	T;T;.;T;.
Sift4G	Uncertain	0.014	D;D;D;D;D
Polyphen		0.030	B;B;B;B;.
Vest4		0.14
MutPred		0.23		Gain of phosphorylation at P58 (P = 0.0025);Gain of phosphorylation at P58 (P = 0.0025);Gain of phosphorylation at P58 (P = 0.0025);Gain of phosphorylation at P58 (P = 0.0025);Gain of phosphorylation at P58 (P = 0.0025);
MVP		0.068
MPC		0.22
ClinPred		0.13	T
GERP RS		0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.085

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: rs775394719; hg19: chr19-45394844;