chr22-42121918-T-A

Variant names:

• chr22-42121918-T-A
• rs5751222
• ENST00000417327.5:n.531-2129T>A

Variant summary

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

The ENST00000417327.5(NDUFA6-DT):​n.531-2129T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,228 control chromosomes in the GnomAD database, including 3,136 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 0.18 (3136 hom., cov: 32)
• Consequence: NDUFA6-DT ENST00000417327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA6-DT	NR_034118.2	n.668-2129T>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA6-DT	ENST00000417327.5	n.531-2129T>A		intron_variant	Intron 2 of 3	5
NDUFA6-DT	ENST00000434834.5	n.314-2129T>A		intron_variant	Intron 2 of 4	5
NDUFA6-DT	ENST00000439129.5	n.670-2129T>A		intron_variant	Intron 3 of 6	5

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28168 AN: 152110 Hom.: 3138 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.185 AC: 28154 AN: 152228 Hom.: 3136 Cov.: 32 AF XY: 0.180 AC XY: 13412 AN XY: 74436

African (AFR) AF: 0.117 AC: 4881 AN: 41556

American (AMR) AF: 0.149 AC: 2270 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3470

East Asian (EAS) AF: 0.516 AC: 2673 AN: 5180

South Asian (SAS) AF: 0.161 AC: 778 AN: 4822

European-Finnish (FIN) AF: 0.113 AC: 1201 AN: 10614

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14829 AN: 67988

Other (OTH) AF: 0.175 AC: 369 AN: 2112

Alfa AF: 0.194 Hom.: 370

Bravo AF: 0.186

Asia WGS AF: 0.281 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.60
PhyloP100		0.80

Splicing

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

Other links and lift over

dbSNP: rs5751222; hg19: chr22-42517922;