22-42132375-G-C

Variant names:

• chr22-42132375-G-C
• rs1080985
• ENST00000617009.4:n.166G>C

Variant summary

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

The ENST00000617009.4(NDUFA6-DT):​n.166G>C 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 0.194 in 150,524 control chromosomes in the GnomAD database, including 4,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (★).

• Frequency:
  • Genomes: 𝑓 0.19 (4004 hom., cov: 31)
  • Exomes 𝑓: 0.18 (4 hom.)
• Consequence: NDUFA6-DT ENST00000617009.4 non_coding_transcript_exon
• Clinical Significance: other criteria provided, single submitter O:1
• Conservation: PhyloP100: -0.693

Genes affected

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

ENSG00000227370 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 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	ENST00000617009.4	n.166G>C		non_coding_transcript_exon_variant	Exon 2 of 5	5
NDUFA6-DT	ENST00000621190.1	n.166G>C		non_coding_transcript_exon_variant	Exon 2 of 8	5
NDUFA6-DT	ENST00000439129.5	n.1719-3824G>C		intron_variant	Intron 5 of 6	5
ENSG00000227370	ENST00000417586.1	n.-168G>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29130 AN: 150260 Hom.: 3998 Cov.: 31

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.180 AC: 27 AN: 150 Hom.: 4 Cov.: 0 AF XY: 0.190 AC XY: 22 AN XY: 116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.194 AC: 29140 AN: 150374 Hom.: 4004 Cov.: 31 AF XY: 0.201 AC XY: 14756 AN XY: 73466

Gnomad4 AFR AF: 0.0770

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.220

Alfa AF: 0.128 Hom.: 306

Bravo AF: 0.178

ClinVar

Significance: other

Submissions summary: Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Other:1

Aug 06, 2018

Eurofins Ntd Llc (ga)

Significance: other

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles).

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1080985; hg19: chr22-42528382;