12-4654234-G-C

Position:

• chr12-4654234-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005002.5(NDUFA9):​c.50-58G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,493,716 control chromosomes in the GnomAD database, including 52,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.26 (5486 hom., cov: 33)
  • Exomes 𝑓: 0.26 (47292 hom.)
• Consequence: NDUFA9 NM_005002.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.120

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 12-4654234-G-C is Benign according to our data. Variant chr12-4654234-G-C is described in ClinVar as [Benign]. Clinvar id is 1290676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA9	NM_005002.5	c.50-58G>C		intron_variant		ENST00000266544.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA9	ENST00000266544.10	c.50-58G>C		intron_variant		1	NM_005002.5	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40268 AN: 151982 Hom.: 5489 Cov.: 33

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.262 AC: 351156 AN: 1341616 Hom.: 47292 AF XY: 0.261 AC XY: 172791 AN XY: 663026

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.366

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.265 AC: 40291 AN: 152100 Hom.: 5486 Cov.: 33 AF XY: 0.258 AC XY: 19167 AN XY: 74354

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.298

Alfa AF: 0.268 Hom.: 687

Bravo AF: 0.269

Asia WGS AF: 0.215 AC: 753 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.60
BranchPoint Hunter		1.0

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: rs2302246; hg19: chr12-4763400; COSMIC: COSV56929351; COSMIC: COSV56929351;