Genetic Variant NDUFAF8:c.195+84T>C (chr17-81239762-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001353403.1(NDUFAF8):c.-145T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,395,808 control chromosomes in the GnomAD database, including 145,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 13513 hom., cov: 33)

Exomes 𝑓: 0.45 ( 132127 hom. )

Consequence

NDUFAF8
NM_001353403.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.297

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-81239762-T-C is Benign according to our data. Variant chr17-81239762-T-C is described in ClinVar as [Benign]. Clinvar id is 1263744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF8	NM_001086521.2 link	c.195+84T>C		intron_variant	Intron 2 of 2	ENST00000431388.3	NP_001079990.1	A1L188

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF8	ENST00000431388.3 link	c.195+84T>C		intron_variant	Intron 2 of 2	1	NM_001086521.2	ENSP00000400184.2		A1L188

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57184

AN:

151920

Hom.:

13507

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0899

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.702

Gnomad SAS

AF:

0.558

Gnomad FIN

AF:

0.527

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.394

GnomAD4 exome

AF:

0.451

AC:

560519

AN:

1243770

Hom.:

132127

Cov.:

AF XY:

0.454

AC XY:

280301

AN XY:

617372

show subpopulations

Gnomad4 AFR exome

AF:

0.0715

Gnomad4 AMR exome

AF:

0.643

Gnomad4 ASJ exome

AF:

0.498

Gnomad4 EAS exome

AF:

0.695

Gnomad4 SAS exome

AF:

0.557

Gnomad4 FIN exome

AF:

0.499

Gnomad4 NFE exome

AF:

0.436

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.376

AC:

57201

AN:

152038

Hom.:

13513

Cov.:

AF XY:

0.387

AC XY:

28783

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0898

Gnomad4 AMR

AF:

0.541

Gnomad4 ASJ

AF:

0.507

Gnomad4 EAS

AF:

0.702

Gnomad4 SAS

AF:

0.558

Gnomad4 FIN

AF:

0.527

Gnomad4 NFE

AF:

0.446

Gnomad4 OTH

AF:

0.397

Alfa

AF:

0.415

Hom.:

3734

Bravo

AF:

0.366

Asia WGS

AF:

0.595

AC:

2070

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.0

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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