chr1-235112974-C-T

Variant names:

• chr1-235112974-C-T
• rs4551650
• NM_014765.3:c.393+794G>A

Variant summary

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

The NM_014765.3(TOMM20):​c.393+794G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,092 control chromosomes in the GnomAD database, including 6,074 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 0.25 (6074 hom., cov: 32)
• Consequence: TOMM20 NM_014765.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM20	NM_014765.3	c.393+794G>A		intron_variant	Intron 4 of 4	ENST00000366607.5	NP_055580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM20	ENST00000366607.5	c.393+794G>A		intron_variant	Intron 4 of 4	1	NM_014765.3	ENSP00000355566.4
TOMM20	ENST00000467767.5	n.293+794G>A		intron_variant	Intron 3 of 3	3
TOMM20	ENST00000473132.1	n.359+794G>A		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38009 AN: 151974 Hom.: 6080 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.250 AC: 37997 AN: 152092 Hom.: 6074 Cov.: 32 AF XY: 0.258 AC XY: 19189 AN XY: 74336

African (AFR) AF: 0.0581 AC: 2414 AN: 41518

American (AMR) AF: 0.343 AC: 5244 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3466

East Asian (EAS) AF: 0.273 AC: 1408 AN: 5166

South Asian (SAS) AF: 0.524 AC: 2529 AN: 4824

European-Finnish (FIN) AF: 0.356 AC: 3748 AN: 10534

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21002 AN: 67980

Other (OTH) AF: 0.241 AC: 508 AN: 2106

Alfa AF: 0.285 Hom.: 10096

Bravo AF: 0.233

Asia WGS AF: 0.372 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.78
PhyloP100		-0.36
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: rs4551650; hg19: chr1-235276289;