22-42122378-A-G

Variant names:

• chr22-42122378-A-G
• rs5758589
• ENST00000417327.5:n.531-1669A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000417327.5(NDUFA6-DT):​n.531-1669A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,044 control chromosomes in the GnomAD database, including 26,899 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 0.59 (26899 hom., cov: 32)
• Consequence: NDUFA6-DT ENST00000417327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 21 publications found

Genes affected

NDUFA6-DT (HGNC:45273): (NDUFA6 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000417327.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA6-DT	NR_034118.2		n.668-1669A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA6-DT	ENST00000417327.5	TSL:5	n.531-1669A>G		intron	N/A
	NDUFA6-DT	ENST00000434834.5	TSL:5	n.314-1669A>G		intron	N/A
	NDUFA6-DT	ENST00000439129.5	TSL:5	n.670-1669A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89355 AN: 151926 Hom.: 26861 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.588 AC: 89441 AN: 152044 Hom.: 26899 Cov.: 32 AF XY: 0.584 AC XY: 43446 AN XY: 74334

African (AFR) AF: 0.705 AC: 29257 AN: 41470

American (AMR) AF: 0.490 AC: 7488 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2212 AN: 3472

East Asian (EAS) AF: 0.673 AC: 3479 AN: 5168

South Asian (SAS) AF: 0.542 AC: 2614 AN: 4820

European-Finnish (FIN) AF: 0.500 AC: 5284 AN: 10576

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37268 AN: 67952

Other (OTH) AF: 0.564 AC: 1192 AN: 2112

Alfa AF: 0.572 Hom.: 29368

Bravo AF: 0.590

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.74
PhyloP100		-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5758589; hg19: chr22-42518382;