12-4654238-G-C

Variant names:

• chr12-4654238-G-C
• rs61909964
• NM_005002.5:c.50-54G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005002.5(NDUFA9):​c.50-54G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,521,678 control chromosomes in the GnomAD database, including 758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (131 hom., cov: 33)
  • Exomes 𝑓: 0.027 (627 hom.)
• Consequence: NDUFA9 NM_005002.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.174

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-4654238-G-C is Benign according to our data. Variant chr12-4654238-G-C is described in ClinVar as [Benign]. Clinvar id is 671701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA9	NM_005002.5	c.50-54G>C		intron_variant	Intron 1 of 10	ENST00000266544.10	NP_004993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA9	ENST00000266544.10	c.50-54G>C		intron_variant	Intron 1 of 10	1	NM_005002.5	ENSP00000266544.5
ENSG00000255639	ENST00000648836.1	c.50-54G>C		intron_variant	Intron 1 of 14			ENSP00000497305.1
ENSG00000272921	ENST00000536588.1	n.*50-54G>C		intron_variant	Intron 2 of 6	3		ENSP00000445121.1

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5180 AN: 152148 Hom.: 128 Cov.: 33

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0275 AC: 37626 AN: 1369412 Hom.: 627 AF XY: 0.0270 AC XY: 18279 AN XY: 676516

Gnomad4 AFR exome AF: 0.0641

Gnomad4 AMR exome AF: 0.0140

Gnomad4 ASJ exome AF: 0.0167

Gnomad4 EAS exome AF: 0.000390

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0294

Gnomad4 OTH exome AF: 0.0265

GnomAD4 genome AF: 0.0341 AC: 5199 AN: 152266 Hom.: 131 Cov.: 33 AF XY: 0.0321 AC XY: 2388 AN XY: 74470

Gnomad4 AFR AF: 0.0637

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.00912

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0276

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0317 Hom.: 9

Bravo AF: 0.0350

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.51

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: rs61909964; hg19: chr12-4763404;