rs11301

Positions:

• chr1-235109864-G-A

Variant summary

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

The NM_014765.3(TOMM20):​c.*2200C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,122 control chromosomes in the GnomAD database, including 39,012 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 0.71 (39011 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: TOMM20 NM_014765.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOMM20	NM_014765.3	c.*2200C>T		3_prime_UTR_variant	5/5	ENST00000366607.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM20	ENST00000366607.5	c.*2200C>T		3_prime_UTR_variant	5/5	1	NM_014765.3	P1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107692 AN: 152000 Hom.: 38977 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.663

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.709 AC: 107779 AN: 152118 Hom.: 39011 Cov.: 32 AF XY: 0.708 AC XY: 52669 AN XY: 74352

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.657

Alfa AF: 0.668 Hom.: 33657

Bravo AF: 0.702

Asia WGS AF: 0.566 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.29

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: rs11301; hg19: chr1-235273179;