Genetic Variant NDUFAF8:c.*203C>T (chr17-81241219-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001086521.2(NDUFAF8):c.*203C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 1,352,812 control chromosomes in the GnomAD database, including 972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 78 hom., cov: 32)

Exomes 𝑓: 0.036 ( 894 hom. )

Consequence

NDUFAF8
NM_001086521.2 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.48

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=-0.91).

BP6

Variant 17-81241219-C-T is Benign according to our data. Variant chr17-81241219-C-T is described in ClinVar as [Benign]. Clinvar id is 1225139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0278 (4224/152168) while in subpopulation NFE AF= 0.037 (2514/67996). AF 95% confidence interval is 0.0358. There are 78 homozygotes in gnomad4. There are 2156 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 78 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF8	NM_001086521.2 link	c.*203C>T	3_prime_UTR_variant	Exon 3 of 3	ENST00000431388.3	NP_001079990.1	A1L188
NDUFAF8	NM_001353402.1 link	c.*66C>T	3_prime_UTR_variant	Exon 3 of 3		NP_001340331.1
NDUFAF8	NM_001353403.1 link	c.*66C>T	3_prime_UTR_variant	Exon 3 of 3		NP_001340332.1
NDUFAF8	NR_148426.1 link	n.759C>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.*203C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_001086521.2	ENSP00000400184.2		A1L188

Frequencies

GnomAD3 genomes

AF:

0.0278

AC:

4225

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00688

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0225

Gnomad ASJ

AF:

0.0850

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0184

Gnomad FIN

AF:

0.0525

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0370

Gnomad OTH

AF:

0.0340

GnomAD4 exome

AF:

0.0355

AC:

42650

AN:

1200644

Hom.:

894

Cov.:

AF XY:

0.0354

AC XY:

20494

AN XY:

578612

show subpopulations

Gnomad4 AFR exome

AF:

0.00776

Gnomad4 AMR exome

AF:

0.0252

Gnomad4 ASJ exome

AF:

0.0849

Gnomad4 EAS exome

AF:

0.000124

Gnomad4 SAS exome

AF:

0.0193

Gnomad4 FIN exome

AF:

0.0510

Gnomad4 NFE exome

AF:

0.0372

Gnomad4 OTH exome

AF:

0.0344

GnomAD4 genome

AF:

0.0278

AC:

4224

AN:

152168

Hom.:

Cov.:

AF XY:

0.0290

AC XY:

2156

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00686

Gnomad4 AMR

AF:

0.0224

Gnomad4 ASJ

AF:

0.0850

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0186

Gnomad4 FIN

AF:

0.0525

Gnomad4 NFE

AF:

0.0370

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0345

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.00664

AC:

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

May 22, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.24

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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