rs3813628

Positions:

• chr1-161226376-A-C
• chr1-161226376-A-T

Variant summary

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

The NM_032174.6(TOMM40L):​c.-114A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 869,156 control chromosomes in the GnomAD database, including 52,557 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 0.29 (7165 hom., cov: 27)
  • Exomes 𝑓: 0.35 (45392 hom.)
• Consequence: TOMM40L NM_032174.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

Genes affected

TOMM40L (HGNC:25756): (translocase of outer mitochondrial membrane 40 like) Predicted to enable protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix. Part of protein-containing complex. [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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOMM40L	NM_032174.6	c.-114A>C		5_prime_UTR_variant	2/10	ENST00000367988.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM40L	ENST00000367988.8	c.-114A>C		5_prime_UTR_variant	2/10	2	NM_032174.6	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43297 AN: 150096 Hom.: 7165 Cov.: 27

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.349 AC: 250592 AN: 718940 Hom.: 45392 Cov.: 10 AF XY: 0.347 AC XY: 127073 AN XY: 366192

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.326

Gnomad4 EAS exome AF: 0.535

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.288 AC: 43304 AN: 150216 Hom.: 7165 Cov.: 27 AF XY: 0.289 AC XY: 21206 AN XY: 73272

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.306

Alfa AF: 0.337 Hom.: 9859

Bravo AF: 0.286

Asia WGS AF: 0.434 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs3813628; hg19: chr1-161196166;