rs1056610

Positions:

• chr22-38684073-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020243.5(TOMM22):​c.*232T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 491,696 control chromosomes in the GnomAD database, including 30,753 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 0.37 (11145 hom., cov: 32)
  • Exomes 𝑓: 0.33 (19608 hom.)
• Consequence: TOMM22 NM_020243.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

Genes affected

TOMM22 (HGNC:18002): (translocase of outer mitochondrial membrane 22) The protein encoded by this gene is an integral membrane protein of the mitochondrial outer membrane. The encoded protein interacts with TOMM20 and TOMM40, and forms a complex with several other proteins to import cytosolic preproteins into the mitochondrion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM22	NM_020243.5	c.*232T>C		3_prime_UTR_variant	4/4	ENST00000216034.6	NP_064628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM22	ENST00000216034.6	c.*232T>C		3_prime_UTR_variant	4/4	1	NM_020243.5	ENSP00000216034	P1
TOMM22	ENST00000492561.1	n.695T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56426 AN: 151970 Hom.: 11130 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.331 AC: 112351 AN: 339606 Hom.: 19608 Cov.: 3 AF XY: 0.328 AC XY: 58042 AN XY: 176888

Gnomad4 AFR exome AF: 0.510

Gnomad4 AMR exome AF: 0.253

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.371 AC: 56488 AN: 152090 Hom.: 11145 Cov.: 32 AF XY: 0.369 AC XY: 27462 AN XY: 74332

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.342

Alfa AF: 0.320 Hom.: 8302

Bravo AF: 0.371

Asia WGS AF: 0.389 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1056610; hg19: chr22-39080078;