22-42132969-C-T

Variant names:

• chr22-42132969-C-T
• rs28360521
• ENST00000417586.1:n.427C>T

Variant summary

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

The ENST00000417586.1(ENSG00000227370):​n.427C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 155,106 control chromosomes in the GnomAD database, including 5,004 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 0.22 (4819 hom., cov: 32)
  • Exomes 𝑓: 0.22 (185 hom.)
• Consequence: ENSG00000227370 ENST00000417586.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 26 publications found

Genes affected

ENSG00000227370 (HGNC:):

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 = 0.524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000417586.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000227370	ENST00000417586.1	TSL:6	n.427C>T		non_coding_transcript_exon	Exon 1 of 1
	NDUFA6-DT	ENST00000439129.5	TSL:5	n.1719-3230C>T		intron	N/A
	NDUFA6-DT	ENST00000617009.4	TSL:5	n.394-71C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32719 AN: 150510 Hom.: 4820 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.224 AC: 1005 AN: 4482 Hom.: 185 Cov.: 0 AF XY: 0.232 AC XY: 561 AN XY: 2414

African (AFR) AF: 0.209 AC: 18 AN: 86

American (AMR) AF: 0.186 AC: 16 AN: 86

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 4 AN: 8

East Asian (EAS) AF: 0.737 AC: 174 AN: 236

South Asian (SAS) AF: 0.162 AC: 152 AN: 940

European-Finnish (FIN) AF: 0.143 AC: 66 AN: 462

Middle Eastern (MID) AF: 0.143 AC: 178 AN: 1248

European-Non Finnish (NFE) AF: 0.289 AC: 332 AN: 1150

Other (OTH) AF: 0.244 AC: 65 AN: 266

GnomAD4 genome AF: 0.217 AC: 32717 AN: 150624 Hom.: 4819 Cov.: 32 AF XY: 0.211 AC XY: 15522 AN XY: 73548

African (AFR) AF: 0.219 AC: 8895 AN: 40708

American (AMR) AF: 0.163 AC: 2469 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 857 AN: 3462

East Asian (EAS) AF: 0.541 AC: 2764 AN: 5106

South Asian (SAS) AF: 0.167 AC: 793 AN: 4750

European-Finnish (FIN) AF: 0.112 AC: 1186 AN: 10556

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15042 AN: 67584

Other (OTH) AF: 0.196 AC: 408 AN: 2080

Alfa AF: 0.218 Hom.: 1053

Bravo AF: 0.224

Asia WGS AF: 0.294 AC: 1020 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.68
PhyloP100		-0.086

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs28360521;

hg19: chr22-42528976;