Variant 12-4654234-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.120

Variant links:

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]

NDUFA9 links:

ENSG00000255639 (HGNC:):

ENSG00000255639 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
NDUFA9	NM_005002.5 link	c.50-58G>C		intron_variant	Intron 1 of 10	ENST00000266544.10	NP_004993.1	Q16795

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NDUFA9	ENST00000266544.10 link	c.50-58G>C	intron_variant	Intron 1 of 10	1	NM_005002.5	ENSP00000266544.5	Q16795
ENSG00000255639	ENST00000648836.1 link	c.50-58G>C	intron_variant	Intron 1 of 14			ENSP00000497305.1	A0A3B3ISG8
ENSG00000272921	ENST00000536588.1 link	n.*50-58G>C	intron_variant	Intron 2 of 6	3		ENSP00000445121.1	H0YGX0

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40268

AN:

151982

Hom.:

5489

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.258

AC XY:

19167

AN XY:

74354

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over