rs7972920

Positions:

• chr12-4659453-A-G
• chr12-4659453-A-T

Variant summary

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

The ENST00000266544.10(NDUFA9):​c.552+276A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,082 control chromosomes in the GnomAD database, including 37,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.70 (37587 hom., cov: 31)
• Consequence: NDUFA9 ENST00000266544.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.250

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: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-4659453-A-G is Benign according to our data. Variant chr12-4659453-A-G is described in ClinVar as [Benign]. Clinvar id is 682712.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA9	NM_005002.5	c.552+276A>G		intron_variant		ENST00000266544.10	NP_004993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA9	ENST00000266544.10	c.552+276A>G		intron_variant		1	NM_005002.5	ENSP00000266544	P1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106182 AN: 151964 Hom.: 37563 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.677

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.699 AC: 106257 AN: 152082 Hom.: 37587 Cov.: 31 AF XY: 0.706 AC XY: 52510 AN XY: 74344

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.679

Alfa AF: 0.719 Hom.: 19959

Bravo AF: 0.690

Asia WGS AF: 0.777 AC: 2697 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 14, 2018

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	-0.86
CADD	Benign	5.2
DANN	Benign	0.40

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: rs7972920; hg19: chr12-4768619;