17-81241127-C-T

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

2

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]

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
NDUFAF8NM_001086521.2 linkc.*111C>T 3_prime_UTR_variant Exon 3 of 3 ENST00000431388.3 NP_001079990.1 A1L188
NDUFAF8NM_001353402.1 linkc.340C>T p.Arg114* stop_gained Exon 3 of 3 NP_001340331.1
NDUFAF8NM_001353403.1 linkc.178C>T p.Arg60* stop_gained Exon 3 of 3 NP_001340332.1
NDUFAF8NR_148426.1 linkn.667C>T non_coding_transcript_exon_variant Exon 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NDUFAF8ENST00000431388.3 linkc.*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.:
10
Cov.:
32
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.:
9
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.:
26
Cov.:
30
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.:
10
Cov.:
32
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.:
2
Bravo
AF:
0.00744
Asia WGS
AF:
0.0150
AC:
53
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.

Other links and lift over

dbSNP: rs76221565; hg19: chr17-79214927; API