rs12666974

Positions:

• chr7-123551920-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005000.5(NDUFA5):​c.67-1334A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,052 control chromosomes in the GnomAD database, including 4,801 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4801 hom., cov: 32)
• Consequence: NDUFA5 NM_005000.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

Genes affected

NDUFA5 (HGNC:7688): (NADH:ubiquinone oxidoreductase subunit A5) This nuclear gene encodes a conserved protein that comprises the B13 subunit of complex I of the mitochondrial respiratory chain. The encoded protein localizes to the inner mitochondrial membrane, where it is thought to aid in the transfer of electrons from NADH to ubiquinone. Alternative splicing results in multiple transcript variants. There are numerous pseudogenes of this gene on chromosomes 1, 3, 6, 8, 9, 11, 12, and 16. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA5	NM_005000.5	c.67-1334A>T		intron_variant		ENST00000355749.7	NP_004991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA5	ENST00000355749.7	c.67-1334A>T		intron_variant		1	NM_005000.5	ENSP00000347988.2

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35565 AN: 151934 Hom.: 4811 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.234 AC: 35549 AN: 152052 Hom.: 4801 Cov.: 32 AF XY: 0.241 AC XY: 17869 AN XY: 74272

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.217

Alfa AF: 0.253 Hom.: 806

Bravo AF: 0.216

Asia WGS AF: 0.280 AC: 973 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.53

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: rs12666974; hg19: chr7-123191974;