chr10-100529505-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_005004.4(NDUFB8):c.87C>T(p.Ala29Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A29A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NDUFB8
NM_005004.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00001946

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.242

Publications

0 publications found

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]

NDUFB8 links:

ENSG00000255339 (HGNC:):

ENSG00000255339 links:

HIF1AN (HGNC:17113): (hypoxia inducible factor 1 subunit alpha inhibitor) Enables several functions, including 2-oxoglutarate-dependent dioxygenase activity; NF-kappaB binding activity; and transition metal ion binding activity. Involved in several processes, including negative regulation of Notch signaling pathway; negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; and protein hydroxylation. Located in cytosol; nucleoplasm; and perinuclear region of cytoplasm. Colocalizes with nucleus. [provided by Alliance of Genome Resources, Apr 2022]

HIF1AN links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP7

Synonymous conserved (PhyloP=0.242 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005004.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFB8	NM_005004.4	MANE Select	c.87C>T	p.Ala29Ala	splice_region synonymous	Exon 2 of 5	NP_004995.1	O95169-1
NDUFB8	NM_001284368.1		c.-7C>T		splice_region	Exon 2 of 5	NP_001271297.1	O95169-3
NDUFB8	NM_001284367.2		c.87C>T	p.Ala29Ala	splice_region synonymous	Exon 2 of 5	NP_001271296.1	O95169-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFB8	ENST00000299166.9	TSL:1 MANE Select	c.87C>T	p.Ala29Ala	splice_region synonymous	Exon 2 of 5	ENSP00000299166.4	O95169-1
ENSG00000255339	ENST00000557395.5	TSL:2	n.87C>T		splice_region non_coding_transcript_exon	Exon 2 of 10	ENSP00000456832.1
NDUFB8	ENST00000370322.5	TSL:2	c.-7C>T		splice_region	Exon 2 of 5	ENSP00000359346.1	O95169-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000806

AC:

AN:

248116

AF XY:

0.00000744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459480

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33280

American (AMR)

AF:

0.00

AC:

AN:

43590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111406

Other (OTH)

AF:

0.00

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.6

(source)

DANN

Benign

0.80

PhyloP100

0.24

PromoterAI

-0.029

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over