Genetic Variant NDUFAF8:c.*111C>T (chr17-81241127-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001353402.1(NDUFAF8):c.340C>T(p.Arg114*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,450,946 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0047 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 26 hom. )

Consequence

NDUFAF8
NM_001353402.1 stop_gained

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.860

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 17-81241127-C-T is Benign according to our data. Variant chr17-81241127-C-T is described in ClinVar as [Benign]. Clinvar id is 3059094.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00467 (711/152200) while in subpopulation EAS AF= 0.0355 (184/5186). AF 95% confidence interval is 0.0313. There are 10 homozygotes in gnomad4. There are 380 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF8	NM_001086521.2 link	c.*111C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000431388.3	NP_001079990.1	A1L188
NDUFAF8	NM_001353402.1 link	c.340C>T	p.Arg114*	stop_gained	Exon 3 of 3		NP_001340331.1
NDUFAF8	NM_001353403.1 link	c.178C>T	p.Arg60*	stop_gained	Exon 3 of 3		NP_001340332.1
NDUFAF8	NR_148426.1 link	n.667C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF8	ENST00000431388.3 link	c.*111C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_001086521.2	ENSP00000400184.2		A1L188

Frequencies

GnomAD3 genomes

AF:

0.00465

AC:

707

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0268

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0354

Gnomad SAS

AF:

0.00519

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00670

AC:

774

AN:

115516

Hom.:

AF XY:

0.00651

AC XY:

404

AN XY:

62090

show subpopulations

Gnomad AFR exome

AF:

0.000765

Gnomad AMR exome

AF:

0.0248

Gnomad ASJ exome

AF:

0.000417

Gnomad EAS exome

AF:

0.0356

Gnomad SAS exome

AF:

0.00645

Gnomad FIN exome

AF:

0.000613

Gnomad NFE exome

AF:

0.000353

Gnomad OTH exome

AF:

0.00826

GnomAD4 exome

AF:

0.00195

AC:

2527

AN:

1298746

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1256

AN XY:

633680

show subpopulations

Gnomad4 AFR exome

AF:

0.000561

Gnomad4 AMR exome

AF:

0.0265

Gnomad4 ASJ exome

AF:

0.000336

Gnomad4 EAS exome

AF:

0.0317

Gnomad4 SAS exome

AF:

0.00537

Gnomad4 FIN exome

AF:

0.000416

Gnomad4 NFE exome

AF:

0.000202

Gnomad4 OTH exome

AF:

0.00369

GnomAD4 genome

AF:

0.00467

AC:

711

AN:

152200

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

380

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.0269

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0355

Gnomad4 SAS

AF:

0.00561

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00744

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NDUFAF8-related disorder

Benign:1

Jun 12, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.6

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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