rs776623679

Variant names:

• chr9-122152372-G-A
• rs776623679
• NM_014222.3:c.88C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-122152372-G-A
• chr9-122152372-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014222.3(NDUFA8):​c.88C>T​(p.His30Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDUFA8 NM_014222.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.27

Genes affected

NDUFA8 (HGNC:7692): (NADH:ubiquinone oxidoreductase subunit A8) The protein encoded by this gene belongs to the complex I 19 kDa subunit family. Mammalian complex I is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It plays an important role in transfering electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA8	NM_014222.3	c.88C>T	p.His30Tyr	missense_variant	Exon 2 of 4	ENST00000373768.4	NP_055037.1
NDUFA8	NM_001318195.2	c.88C>T	p.His30Tyr	missense_variant	Exon 2 of 4		NP_001305124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA8	ENST00000373768.4	c.88C>T	p.His30Tyr	missense_variant	Exon 2 of 4	1	NM_014222.3	ENSP00000362873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Benign	0.80
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.049
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.17	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.050	N
REVEL	Uncertain	0.39
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.016	B
Vest4		0.79
MutPred		0.52		Gain of phosphorylation at H30 (P = 0.059);
MVP		0.84
MPC		0.35
ClinPred		0.83	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.39
gMVP		0.73

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

Other links and lift over

dbSNP: rs776623679; hg19: chr9-124914651;