7-123545803-A-T

Position:

• chr7-123545803-A-T

Variant summary

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

The NM_005000.5(NDUFA5):​c.184-127T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 617,704 control chromosomes in the GnomAD database, including 25,755 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 0.28 (6255 hom., cov: 32)
  • Exomes 𝑓: 0.29 (19500 hom.)
• Consequence: NDUFA5 NM_005000.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA5	NM_005000.5	c.184-127T>A		intron_variant		ENST00000355749.7	NP_004991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA5	ENST00000355749.7	c.184-127T>A		intron_variant		1	NM_005000.5	ENSP00000347988	P3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43112 AN: 151772 Hom.: 6259 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.286 AC: 133162 AN: 465814 Hom.: 19500 Cov.: 6 AF XY: 0.284 AC XY: 70526 AN XY: 248434

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.404

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.284 AC: 43124 AN: 151890 Hom.: 6255 Cov.: 32 AF XY: 0.289 AC XY: 21440 AN XY: 74216

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.255

Alfa AF: 0.280 Hom.: 793

Bravo AF: 0.274

Asia WGS AF: 0.283 AC: 978 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.82

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: rs3779262; hg19: chr7-123185857;