7-123545803-A-T

Variant names:

• chr7-123545803-A-T
• rs3779262
• NM_005000.5:c.184-127T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005000.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA5	NM_005000.5	MANE Select	c.184-127T>A		intron	N/A	NP_004991.1	Q16718-1
	NDUFA5	NM_001291304.2		c.382-127T>A		intron	N/A	NP_001278233.1
	NDUFA5	NM_001282420.3		c.184-127T>A		intron	N/A	NP_001269349.1	Q16718-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA5	ENST00000355749.7	TSL:1 MANE Select	c.184-127T>A		intron	N/A	ENSP00000347988.2	Q16718-1
	NDUFA5	ENST00000471770.5	TSL:1	c.184-127T>A		intron	N/A	ENSP00000417142.1	Q16718-2
	NDUFA5	ENST00000678090.1		c.271-127T>A		intron	N/A	ENSP00000503587.1	A0A7I2V3L8

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

African (AFR) AF: 0.287 AC: 3256 AN: 11330

American (AMR) AF: 0.291 AC: 4198 AN: 14440

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 3671 AN: 13880

East Asian (EAS) AF: 0.316 AC: 8834 AN: 27918

South Asian (SAS) AF: 0.269 AC: 11173 AN: 41476

European-Finnish (FIN) AF: 0.404 AC: 11455 AN: 28362

Middle Eastern (MID) AF: 0.198 AC: 385 AN: 1944

European-Non Finnish (NFE) AF: 0.276 AC: 82896 AN: 300774

Other (OTH) AF: 0.284 AC: 7294 AN: 25690

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

African (AFR) AF: 0.277 AC: 11476 AN: 41458

American (AMR) AF: 0.283 AC: 4323 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3462

East Asian (EAS) AF: 0.321 AC: 1659 AN: 5170

South Asian (SAS) AF: 0.264 AC: 1275 AN: 4828

European-Finnish (FIN) AF: 0.407 AC: 4288 AN: 10530

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18329 AN: 67870

Other (OTH) AF: 0.255 AC: 539 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3779262; hg19: chr7-123185857;