1-235109879-T-C

Position:

• chr1-235109879-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014765.3(TOMM20):​c.*2185A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,202 control chromosomes in the GnomAD database, including 2,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2586 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TOMM20 NM_014765.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

Genes affected

TOMM20 (HGNC:20947): (translocase of outer mitochondrial membrane 20) Enables protein-transporting ATPase activity and unfolded protein binding activity. Involved in protein targeting to mitochondrion. Located in mitochondria-associated endoplasmic reticulum membrane and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-235109879-T-C is Benign according to our data. Variant chr1-235109879-T-C is described in ClinVar as [Benign]. Clinvar id is 1181185.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOMM20	NM_014765.3	c.*2185A>G		3_prime_UTR_variant	5/5	ENST00000366607.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM20	ENST00000366607.5	c.*2185A>G		3_prime_UTR_variant	5/5	1	NM_014765.3	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26455 AN: 152080 Hom.: 2578 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.0927

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.174 AC: 26480 AN: 152198 Hom.: 2586 Cov.: 32 AF XY: 0.170 AC XY: 12688 AN XY: 74420

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.175

Alfa AF: 0.0721 Hom.: 85

Bravo AF: 0.178

Asia WGS AF: 0.0730 AC: 258 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

This variant is associated with the following publications: (PMID: 27853382) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.63
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7930; hg19: chr1-235273194;