chr22-42126390-G-A

Position:

• chr22-42126390-G-A

Variant summary

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

The ENST00000439129.5(NDUFA6-DT):​n.1718+983G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 648,100 control chromosomes in the GnomAD database, including 17,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.19 (3782 hom., cov: 32)
  • Exomes 𝑓: 0.21 (13793 hom.)
• Consequence: NDUFA6-DT ENST00000439129.5 intron, non_coding_transcript
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.151

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA6-DT	ENST00000439129.5	n.1718+983G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28373 AN: 150378 Hom.: 3786 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.211 AC: 105074 AN: 497606 Hom.: 13793 AF XY: 0.210 AC XY: 53900 AN XY: 256990

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.188 AC: 28356 AN: 150494 Hom.: 3782 Cov.: 32 AF XY: 0.183 AC XY: 13467 AN XY: 73488

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.175

Alfa AF: 0.107 Hom.: 194

Bravo AF: 0.191

Asia WGS AF: 0.285 AC: 986 AN: 3456

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

drug response, no assertion criteria provided

research

Bruce Budowle Laboratory, University of North Texas Health Science Center

Apr 28, 2018

- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28371738; hg19: chr22-42522392;