NM_005002.5:c.7G>C

Variant names:

• chr12-4649133-G-C
• rs201653293
• NM_005002.5:c.7G>C

Variant summary

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

The NM_005002.5(NDUFA9):​c.7G>C​(p.Ala3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: NDUFA9 NM_005002.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27

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:):

AKAP3 (HGNC:373): (A-kinase anchoring protein 3) This gene encodes a member of A-kinase anchoring proteins (AKAPs), a family of functionally related proteins that target protein kinase A to discrete locations within the cell. The encoded protein is reported to participate in protein-protein interactions with the R-subunit of the protein kinase A as well as sperm-associated proteins. This protein is expressed in spermatozoa and localized to the acrosomal region of the sperm head as well as the length of the principal piece. It may function as a regulator of motility, capacitation, and the acrosome reaction. [provided by RefSeq, May 2013]

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=0.3255642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA9	NM_005002.5	c.7G>C	p.Ala3Pro	missense_variant	Exon 1 of 11	ENST00000266544.10	NP_004993.1
AKAP3	NM_001278309.2	c.-633C>G		upstream_gene_variant		ENST00000228850.6	NP_001265238.2
AKAP3	NM_006422.4	c.-611C>G		upstream_gene_variant			NP_006413.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA9	ENST00000266544.10	c.7G>C	p.Ala3Pro	missense_variant	Exon 1 of 11	1	NM_005002.5	ENSP00000266544.5
ENSG00000255639	ENST00000648836.1	c.7G>C	p.Ala3Pro	missense_variant	Exon 1 of 15			ENSP00000497305.1
ENSG00000272921	ENST00000536588.1	n.*50-5159G>C		intron_variant	Intron 2 of 6	3		ENSP00000445121.1
AKAP3	ENST00000228850.6	c.-633C>G		upstream_gene_variant		5	NM_001278309.2	ENSP00000228850.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T;.
Eigen	Benign	-0.052
Eigen_PC	Benign	0.058
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.020	D;.
Polyphen		0.071	B;.
Vest4		0.61
MutPred		0.30		Gain of glycosylation at A3 (P = 0.0148);Gain of glycosylation at A3 (P = 0.0148);
MVP		0.77
MPC		0.56
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.61
gMVP		0.80

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: rs201653293; hg19: chr12-4758299;