7-22816987-C-T

Variant names:

• chr7-22816987-C-T
• rs2286503
• NM_019059.5:c.152+1013G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019059.5(TOMM7):​c.152+1013G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 152,018 control chromosomes in the GnomAD database, including 19,261 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (19261 hom., cov: 32)
• Consequence: TOMM7 NM_019059.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• Publications: 18 publications found

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]

TOMM7 Gene-Disease associations (from GenCC):

• Garg-Mishra progeroid syndrome

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM7	NM_019059.5	c.152+1013G>A		intron_variant	Intron 2 of 2	ENST00000358435.9	NP_061932.1
TOMM7	NR_168014.1	n.178+1013G>A		intron_variant	Intron 2 of 2
TOMM7	NR_168015.1	n.130-3802G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM7	ENST00000358435.9	c.152+1013G>A		intron_variant	Intron 2 of 2	1	NM_019059.5	ENSP00000351214.4

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72806 AN: 151900 Hom.: 19232 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.432

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.480 AC: 72896 AN: 152018 Hom.: 19261 Cov.: 32 AF XY: 0.483 AC XY: 35883 AN XY: 74300

African (AFR) AF: 0.680 AC: 28184 AN: 41446

American (AMR) AF: 0.452 AC: 6913 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3468

East Asian (EAS) AF: 0.820 AC: 4246 AN: 5180

South Asian (SAS) AF: 0.535 AC: 2578 AN: 4820

European-Finnish (FIN) AF: 0.410 AC: 4326 AN: 10550

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.355 AC: 24127 AN: 67962

Other (OTH) AF: 0.431 AC: 908 AN: 2108

Alfa AF: 0.402 Hom.: 18140

Bravo AF: 0.495

Asia WGS AF: 0.649 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.75
DANN	Benign	0.94
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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: rs2286503; hg19: chr7-22856606;