22-42132027-CTTTTTTTTTTTTT-CTTTTTTTTTTTTTT

Variant names:

• chr22-42132027-C-CT
• rs267608321
• ENST00000439129.5:n.1719-4172_1719-4171insT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000439129.5(NDUFA6-DT):​n.1719-4172_1719-4171insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 121,848 control chromosomes in the GnomAD database, including 144 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.027 (144 hom., cov: 27)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: NDUFA6-DT ENST00000439129.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA6-DT	ENST00000439129.5	n.1719-4172_1719-4171insT		intron_variant	Intron 5 of 6	5
NDUFA6-DT	ENST00000617009.4	n.-4_-3insT		upstream_gene_variant		5
NDUFA6-DT	ENST00000621190.1	n.-4_-3insT		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 3287 AN: 121852 Hom.: 144 Cov.: 27

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.00496

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0146

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.00565

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0232

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0270 AC: 3288 AN: 121844 Hom.: 144 Cov.: 27 AF XY: 0.0258 AC XY: 1473 AN XY: 57198

African (AFR) AF: 0.0643 AC: 1997 AN: 31054

American (AMR) AF: 0.0149 AC: 170 AN: 11402

Ashkenazi Jewish (ASJ) AF: 0.0146 AC: 47 AN: 3230

East Asian (EAS) AF: 0.0286 AC: 126 AN: 4408

South Asian (SAS) AF: 0.00569 AC: 22 AN: 3868

European-Finnish (FIN) AF: 0.0123 AC: 60 AN: 4888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.0137 AC: 823 AN: 60274

Other (OTH) AF: 0.0232 AC: 39 AN: 1682

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs267608321; hg19: -;