Genetic Variant NDUFA6-DT:n.166G>C (chr22-42132375-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

other criteria provided, single submitter O:1

Conservation

PhyloP100: -0.693

Publications

123 publications found

Variant links:

Genes affected

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

NDUFA6-DT links:

ENSG00000227370 (HGNC:):

ENSG00000227370 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000617009.4. 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
NDUFA6-DT	ENST00000617009.4	TSL:5	n.166G>C	non_coding_transcript_exon	Exon 2 of 5
NDUFA6-DT	ENST00000621190.1	TSL:5	n.166G>C	non_coding_transcript_exon	Exon 2 of 8
NDUFA6-DT	ENST00000439129.5	TSL:5	n.1719-3824G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29130

AN:

150260

Hom.:

3998

Cov.:

show subpopulations

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:

AN:

150

Hom.:

Cov.:

AF XY:

0.190

AC XY:

AN XY:

116

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.205

AC:

AN:

122

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.194

AC:

29140

AN:

150374

Hom.:

4004

Cov.:

AF XY:

0.201

AC XY:

14756

AN XY:

73466

show subpopulations

African (AFR)

AF:

0.0770

AC:

3135

AN:

40726

American (AMR)

AF:

0.227

AC:

3433

AN:

15144

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

578

AN:

3468

East Asian (EAS)

AF:

0.115

AC:

585

AN:

5104

South Asian (SAS)

AF:

0.253

AC:

1199

AN:

4744

European-Finnish (FIN)

AF:

0.358

AC:

3743

AN:

10448

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.234

AC:

15791

AN:

67466

Other (OTH)

AF:

0.220

AC:

457

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

907

1815

2722

3630

4537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.128

Hom.:

306

Bravo

AF:

0.178

ClinVar

ClinVar submissions

Significance:other

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.81

(source)

PhyloP100

-0.69

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over