Variant 22-42086214-AG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5

The NM_002490.6(NDUFA6):c.355del(p.Leu119TyrfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

NDUFA6
NM_002490.6 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

NDUFA6 (HGNC:7690): (NADH:ubiquinone oxidoreductase subunit A6) This gene encodes a member of the LYR family of proteins that contain a highly conserved tripeptide (LYR) motif near the N-terminus. The encoded protein is an accessory subunit of NADH: ubiquinone oxidorerductase (Complex I), which is the largest enzyme of the mitochondrial membrane respiratory chain. Complex I functions in electron transfer from NADH to the respiratory chain. [provided by RefSeq, Oct 2016]

NDUFA6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0827 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-42086214-AG-A is Pathogenic according to our data. Variant chr22-42086214-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 549666.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA6	NM_002490.6 linkuse as main transcript	c.355del	p.Leu119TyrfsTer20	frameshift_variant	3/3	ENST00000498737.8	NP_002481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NDUFA6	ENST00000498737.8 linkuse as main transcript	c.355del	p.Leu119TyrfsTer20	frameshift_variant	3/3	1	NM_002490.6	ENSP00000418842	P1
NDUFA6	ENST00000617763.1 linkuse as main transcript	c.433del	p.Leu145TyrfsTer20	frameshift_variant	3/3	1		ENSP00000482543
NDUFA6	ENST00000470753.1 linkuse as main transcript	c.184del	p.Leu62TyrfsTer20	frameshift_variant	2/2	2		ENSP00000473478

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251488

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Mitochondrial complex 1 deficiency, nuclear type 33

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 13, 2018

- -

Mitochondrial disease

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Wellcome Centre for Mitochondrial Research, Newcastle University

Jul 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over