rs371563487

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_005004.4(NDUFB8):​c.442G>T​(p.Asp148Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NDUFB8
NM_005004.4 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.90
Variant links:
Genes affected
NDUFB8 (HGNC:7703): (NADH:ubiquinone oxidoreductase subunit B8) Involved in mitochondrial respiratory chain complex I assembly. Located in endoplasmic reticulum and mitochondrion. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency 32. Biomarker of Alzheimer's disease and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a chain NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial (size 157) in uniprot entity NDUB8_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_005004.4
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21284148).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NDUFB8NM_005004.4 linkc.442G>T p.Asp148Tyr missense_variant Exon 4 of 5 ENST00000299166.9 NP_004995.1 O95169-1
NDUFB8NM_001284367.2 linkc.442G>T p.Asp148Tyr missense_variant Exon 4 of 5 NP_001271296.1 O95169-2
NDUFB8NM_001284368.1 linkc.349G>T p.Asp117Tyr missense_variant Exon 4 of 5 NP_001271297.1 O95169-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NDUFB8ENST00000299166.9 linkc.442G>T p.Asp148Tyr missense_variant Exon 4 of 5 1 NM_005004.4 ENSP00000299166.4 O95169-1
ENSG00000255339ENST00000557395.5 linkn.442G>T non_coding_transcript_exon_variant Exon 4 of 10 2 ENSP00000456832.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000404
AC:
1
AN:
247242
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000554
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457630
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725268
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
17
DANN
Benign
0.94
DEOGEN2
Benign
0.23
T;.;.
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.36
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.63
T;T;.
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;.;L
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-3.1
D;D;D
REVEL
Benign
0.12
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.0070
D;D;D
Polyphen
0.60
P;.;.
Vest4
0.33
MutPred
0.48
Loss of phosphorylation at Y153 (P = 0.1313);.;Loss of phosphorylation at Y153 (P = 0.1313);
MVP
0.30
MPC
0.44
ClinPred
0.60
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.37
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs371563487; hg19: chr10-102286182; API