Genetic Variant NDUFAF8:p.Phe18SerfsTer32 (chr17-81239402-C-CCGCCTCCG) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_001086521.2(NDUFAF8):c.45_52dupCCGCGCCT(p.Phe18SerfsTer32) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000495 in 1,211,936 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

NDUFAF8
NM_001086521.2 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 1.79

Variant links:

Genes affected

NDUFAF8 (HGNC:33551): (NADH:ubiquinone oxidoreductase complex assembly factor 8) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Implicated in nuclear type mitochondrial complex I deficiency 34. [provided by Alliance of Genome Resources, Apr 2022]

NDUFAF8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-81239402-C-CCGCCTCCG is Pathogenic according to our data. Variant chr17-81239402-C-CCGCCTCCG is described in ClinVar as [Pathogenic]. Clinvar id is 691644.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF8	NM_001086521.2 link	c.45_52dupCCGCGCCT	p.Phe18SerfsTer32	frameshift_variant	Exon 1 of 3	ENST00000431388.3	NP_001079990.1	A1L188
NDUFAF8	NM_001353402.1 link	c.45_52dupCCGCGCCT	p.Phe18SerfsTer32	frameshift_variant	Exon 1 of 3		NP_001340331.1
NDUFAF8	NM_001353403.1 link	c.-379_-372dupCCGCGCCT		5_prime_UTR_variant	Exon 1 of 3		NP_001340332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF8	ENST00000431388.3 link	c.45_52dupCCGCGCCT	p.Phe18SerfsTer32	frameshift_variant	Exon 1 of 3	1	NM_001086521.2	ENSP00000400184.2		A1L188

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000495

AC:

AN:

1211936

Hom.:

Cov.:

AF XY:

0.00000514

AC XY:

AN XY:

583876

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:

0.00000606

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mitochondrial disease

Pathogenic:1

Oct 09, 2019

Wellcome Centre for Mitochondrial Research, Newcastle University

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mitochondrial complex 1 deficiency, nuclear type 34

Pathogenic:1

Feb 19, 2020

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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