Variant rs4073054 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032174.6(TOMM40L):c.*1602C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,420,154 control chromosomes in the GnomAD database, including 307,756 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 0.69 ( 36417 hom., cov: 31)

Exomes 𝑓: 0.65 ( 271339 hom. )

Consequence

TOMM40L
NM_032174.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.285

Variant links:

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]

TOMM40L links:

NR1I3 (HGNC:7969): (nuclear receptor subfamily 1 group I member 3) This gene encodes a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. The protein binds to DNA as a monomer or a heterodimer with the retinoid X receptor and regulates the transcription of target genes involved in drug metabolism and bilirubin clearance, such as cytochrome P450 family members. Unlike most nuclear receptors, this transcriptional regulator is constitutively active in the absence of ligand but is regulated by both agonists and inverse agonists. Ligand binding results in translocation of this protein to the nucleus, where it activates or represses target gene transcription. These ligands include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs. In addition to drug metabolism, the CAR protein is also reported to regulate genes involved in glucose metabolism, lipid metabolism, cell proliferation, and circadian clock regulation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

NR1I3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40L	NM_032174.6 link	c.*1602C>A		3_prime_UTR_variant	10/10	ENST00000367988.8	NP_115550.2	Q969M1-1
NR1I3	NM_005122.5 link	c.917+116G>T		intron_variant		ENST00000367983.9	NP_005113.1	Q14994-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40L	ENST00000367988.8 link	c.*1602C>A		3_prime_UTR_variant	10/10	2	NM_032174.6	ENSP00000356967.3		Q969M1-1
NR1I3	ENST00000367983.9 link	c.917+116G>T		intron_variant		1	NM_005122.5	ENSP00000356962.5		Q14994-2

Frequencies

GnomAD3 genomes

AF:

0.686

AC:

104291

AN:

151918

Hom.:

36355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.775

Gnomad AMI

AF:

0.589

Gnomad AMR

AF:

0.714

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.909

Gnomad SAS

AF:

0.752

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.618

Gnomad OTH

AF:

0.672

GnomAD4 exome

AF:

0.650

AC:

824427

AN:

1268118

Hom.:

271339

Cov.:

AF XY:

0.651

AC XY:

411892

AN XY:

632880

show subpopulations

Gnomad4 AFR exome

AF:

0.783

Gnomad4 AMR exome

AF:

0.777

Gnomad4 ASJ exome

AF:

0.639

Gnomad4 EAS exome

AF:

0.929

Gnomad4 SAS exome

AF:

0.745

Gnomad4 FIN exome

AF:

0.621

Gnomad4 NFE exome

AF:

0.622

Gnomad4 OTH exome

AF:

0.673

GnomAD4 genome

AF:

0.687

AC:

104410

AN:

152036

Hom.:

36417

Cov.:

AF XY:

0.690

AC XY:

51250

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.775

Gnomad4 AMR

AF:

0.714

Gnomad4 ASJ

AF:

0.635

Gnomad4 EAS

AF:

0.909

Gnomad4 SAS

AF:

0.752

Gnomad4 FIN

AF:

0.628

Gnomad4 NFE

AF:

0.618

Gnomad4 OTH

AF:

0.676

Alfa

AF:

0.634

Hom.:

41868

Bravo

AF:

0.701

Asia WGS

AF:

0.831

AC:

2886

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

0.79

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over