rs4551650

Positions:

• chr1-235112974-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• 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/exons	MANE	Protein	UniProt
TOMM20	NM_014765.3	c.393+794G>A		intron_variant		ENST00000366607.5	NP_055580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM20	ENST00000366607.5	c.393+794G>A		intron_variant		1	NM_014765.3	ENSP00000355566	P1
TOMM20	ENST00000467767.5	n.293+794G>A		intron_variant, non_coding_transcript_variant		3
TOMM20	ENST00000473132.1	n.359+794G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.241

Alfa AF: 0.292 Hom.: 7109

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

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: rs4551650; hg19: chr1-235276289;