12-4654183-C-T

Position:

• chr12-4654183-C-T

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.50-109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,056,770 control chromosomes in the GnomAD database, including 147,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18249 hom., cov: 33)
  • Exomes 𝑓: 0.53 (129396 hom.)
• Consequence: NDUFA9 NM_005002.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.557

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 12-4654183-C-T is Benign according to our data. Variant chr12-4654183-C-T is described in ClinVar as [Benign]. Clinvar id is 1232811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA9	NM_005002.5	c.50-109C>T		intron_variant		ENST00000266544.10	NP_004993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA9	ENST00000266544.10	c.50-109C>T		intron_variant		1	NM_005002.5	ENSP00000266544.5
ENSG00000255639	ENST00000648836.1	c.50-109C>T		intron_variant				ENSP00000497305.1
ENSG00000272921	ENST00000536588.1	n.*50-109C>T		intron_variant		3		ENSP00000445121.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72485 AN: 151962 Hom.: 18245 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.532 AC: 480995 AN: 904690 Hom.: 129396 AF XY: 0.530 AC XY: 241484 AN XY: 455640

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.484

Gnomad4 SAS exome AF: 0.507

Gnomad4 FIN exome AF: 0.641

Gnomad4 NFE exome AF: 0.539

Gnomad4 OTH exome AF: 0.506

GnomAD4 genome AF: 0.477 AC: 72514 AN: 152080 Hom.: 18249 Cov.: 33 AF XY: 0.483 AC XY: 35881 AN XY: 74342

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.443

Alfa AF: 0.500 Hom.: 2467

Bravo AF: 0.462

Asia WGS AF: 0.466 AC: 1617 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	-0.74
CADD	Benign	2.8
DANN	Benign	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: rs2302247; hg19: chr12-4763349; COSMIC: COSV56932982; COSMIC: COSV56932982;