rs756216768

Variant names:

• chr12-4649134-C-G
• rs756216768
• NM_005002.5:c.8C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-4649134-C-G
• chr12-4649134-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005002.5(NDUFA9):​c.8C>G​(p.Ala3Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,452,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NDUFA9 NM_005002.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

Genes affected

NDUFA9 (HGNC:7693): (NADH:ubiquinone oxidoreductase subunit A9) The encoded protein is a subunit of the hydrophobic protein fraction of the NADH:ubiquinone oxidoreductase (complex I), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane. A pseudogene has been identified on chromosome 12. [provided by RefSeq, May 2010]

ENSG00000255639 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3755862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA9	NM_005002.5	c.8C>G	p.Ala3Gly	missense_variant	Exon 1 of 11	ENST00000266544.10	NP_004993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA9	ENST00000266544.10	c.8C>G	p.Ala3Gly	missense_variant	Exon 1 of 11	1	NM_005002.5	ENSP00000266544.5
ENSG00000255639	ENST00000648836.1	c.8C>G	p.Ala3Gly	missense_variant	Exon 1 of 15			ENSP00000497305.1
ENSG00000272921	ENST00000536588.1	n.*50-5158C>G		intron_variant	Intron 2 of 6	3		ENSP00000445121.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452318 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721288

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Uncertain	-0.096	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.2	N;.
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.022	D;.
Polyphen		0.91	P;.
Vest4		0.48
MutPred		0.26		Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);
MVP		0.77
MPC		0.28
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.43
gMVP		0.54

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: rs756216768; hg19: chr12-4758300;