chr1-235129054-C-T

Variant names:

• chr1-235129054-C-T
• rs17523127
• NM_014765.3:c.-339G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014765.3(TOMM20):​c.-339G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 302,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: TOMM20 NM_014765.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM20	NM_014765.3	c.-339G>A		upstream_gene_variant		ENST00000366607.5	NP_055580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM20	ENST00000366607.5	c.-339G>A		upstream_gene_variant		1	NM_014765.3	ENSP00000355566.4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152070 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000663 AC: 1 AN: 150904 Hom.: 0 AF XY: 0.0000124 AC XY: 1 AN XY: 80512

African (AFR) AF: 0.00 AC: 0 AN: 4006

American (AMR) AF: 0.00 AC: 0 AN: 5572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4176

East Asian (EAS) AF: 0.00 AC: 0 AN: 6904

South Asian (SAS) AF: 0.00 AC: 0 AN: 22630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 678

European-Non Finnish (NFE) AF: 0.0000111 AC: 1 AN: 90384

Other (OTH) AF: 0.00 AC: 0 AN: 8558

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152070 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74260

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.81
PhyloP100		-3.0
PromoterAI		-0.026	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17523127; hg19: chr1-235292369;