Variant 5-140644233-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018502.5(TMCO6):c.1200+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,594,126 control chromosomes in the GnomAD database, including 154,937 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 0.41 ( 13375 hom., cov: 32)

Exomes 𝑓: 0.44 ( 141562 hom. )

Consequence

TMCO6
NM_018502.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.354

Variant links:

Genes affected

TMCO6 (HGNC:28814): (transmembrane and coiled-coil domains 6) Predicted to enable nuclear import signal receptor activity. Predicted to be involved in protein import into nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMCO6 links:

NDUFA2 (HGNC:7685): (NADH:ubiquinone oxidoreductase subunit A2) The encoded protein is a subunit of the hydrophobic protein fraction of the NADH:ubiquinone oxidoreductase (complex 1), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane, and may be involved in regulating complex I activity or its assembly via assistance in redox processes. Mutations in this gene are associated with Leigh syndrome, an early-onset progressive neurodegenerative disorder. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

NDUFA2 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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCO6	NM_018502.5 linkuse as main transcript	c.1200+39C>T		intron_variant		ENST00000394671.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCO6	ENST00000394671.8 linkuse as main transcript	c.1200+39C>T		intron_variant		2	NM_018502.5	A1	Q96DC7-1

Frequencies

GnomAD3 genomes

AF:

0.413

AC:

62813

AN:

151930

Hom.:

13365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.773

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.493

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.426

GnomAD3 exomes

AF:

0.434

AC:

108057

AN:

249160

Hom.:

23826

AF XY:

0.436

AC XY:

58986

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.353

Gnomad AMR exome

AF:

0.432

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.509

Gnomad SAS exome

AF:

0.458

Gnomad FIN exome

AF:

0.350

Gnomad NFE exome

AF:

0.442

Gnomad OTH exome

AF:

0.428

GnomAD4 exome

AF:

0.442

AC:

637168

AN:

1442078

Hom.:

141562

Cov.:

AF XY:

0.443

AC XY:

318601

AN XY:

718594

show subpopulations

Gnomad4 AFR exome

AF:

0.357

Gnomad4 AMR exome

AF:

0.431

Gnomad4 ASJ exome

AF:

0.445

Gnomad4 EAS exome

AF:

0.475

Gnomad4 SAS exome

AF:

0.462

Gnomad4 FIN exome

AF:

0.357

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.413

AC:

62846

AN:

152048

Hom.:

13375

Cov.:

AF XY:

0.410

AC XY:

30498

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.350

Gnomad4 AMR

AF:

0.428

Gnomad4 ASJ

AF:

0.445

Gnomad4 EAS

AF:

0.493

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.347

Gnomad4 NFE

AF:

0.443

Gnomad4 OTH

AF:

0.423

Alfa

AF:

0.444

Hom.:

21667

Bravo

AF:

0.419

Asia WGS

AF:

0.391

AC:

1362

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.6

DANN

Benign

0.62

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