NM_019059.5:c.23C>T

Variant names:

• chr7-22822757-G-A
• NM_019059.5:c.23C>T

Variant summary

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

The NM_019059.5(TOMM7):​c.23C>T​(p.Ala8Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A8D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TOMM7 NM_019059.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32

Genes affected

TOMM7 (HGNC:21648): (translocase of outer mitochondrial membrane 7) This gene encodes a subunit of the translocase of the outer mitochondrial membrane. The encoded protein regulates the assembly and stability of the translocase complex. [provided by RefSeq, Oct 2012]

ENSG00000286703 (HGNC:):

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=0.24031794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM7	NM_019059.5	c.23C>T	p.Ala8Val	missense_variant	Exon 1 of 3	ENST00000358435.9	NP_061932.1
TOMM7	NR_168014.1	n.93C>T		non_coding_transcript_exon_variant	Exon 1 of 3
TOMM7	NR_168015.1	n.93C>T		non_coding_transcript_exon_variant	Exon 1 of 2
LOC112267993	XR_002956543.2	n.-200G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM7	ENST00000358435.9	c.23C>T	p.Ala8Val	missense_variant	Exon 1 of 3	1	NM_019059.5	ENSP00000351214.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727238

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T;T;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.84	T
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.87	N;N;.
REVEL	Benign	0.074
Sift	Benign	0.29	T;T;.
Sift4G	Benign	0.14	T;T;T
Polyphen		0.099	B;.;.
Vest4		0.36
MutPred		0.21		Gain of methylation at K9 (P = 0.0351);Gain of methylation at K9 (P = 0.0351);Gain of methylation at K9 (P = 0.0351);
MVP		0.12
MPC		0.12
ClinPred		0.96	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-22862376;