Genetic Variant NDUFA7:p.Pro100Pro (chr19-8311547-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005001.5(NDUFA7):c.300C>T(p.Pro100Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,611,872 control chromosomes in the GnomAD database, including 27,727 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 0.16 ( 2232 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25495 hom. )

Consequence

NDUFA7
NM_005001.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

30 publications found

Variant links:

Genes affected

NDUFA7 (HGNC:7691): (NADH:ubiquinone oxidoreductase subunit A7) This gene encodes a subunit of NADH:ubiquinone oxidoreductase (complex I), which is a multiprotein complex located in the inner mitochondrial membrane. Complex I functions in the transfer of electrons from NADH to the respiratory chain. [provided by RefSeq, Mar 2011]

NDUFA7 links:

ENSG00000167774 (HGNC:):

ENSG00000167774 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP7

Synonymous conserved (PhyloP=-1.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA7	NM_005001.5 link	c.300C>T	p.Pro100Pro	synonymous_variant	Exon 4 of 4	ENST00000301457.3	NP_004992.2	O95182
NDUFA7	NR_135539.2 link	n.317C>T		non_coding_transcript_exon_variant	Exon 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA7	ENST00000301457.3 link	c.300C>T	p.Pro100Pro	synonymous_variant	Exon 4 of 4	1	NM_005001.5	ENSP00000301457.1		O95182
ENSG00000167774	ENST00000598884.1 link	n.300C>T		non_coding_transcript_exon_variant	Exon 4 of 5	4		ENSP00000470609.1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23679

AN:

152066

Hom.:

2233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0511

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.0758

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.195

GnomAD2 exomes

AF:

0.181

AC:

44832

AN:

247198

AF XY:

0.173

show subpopulations

Gnomad AFR exome

AF:

0.0433

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.181

AC:

264190

AN:

1459688

Hom.:

25495

Cov.:

AF XY:

0.177

AC XY:

128717

AN XY:

726098

show subpopulations

African (AFR)

AF:

0.0428

AC:

1430

AN:

33430

American (AMR)

AF:

0.291

AC:

12945

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

4864

AN:

26084

East Asian (EAS)

AF:

0.198

AC:

7828

AN:

39552

South Asian (SAS)

AF:

0.0671

AC:

5774

AN:

86080

European-Finnish (FIN)

AF:

0.190

AC:

10109

AN:

53342

Middle Eastern (MID)

AF:

0.184

AC:

1026

AN:

5564

European-Non Finnish (NFE)

AF:

0.188

AC:

209381

AN:

1110840

Other (OTH)

AF:

0.180

AC:

10833

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

10145

20291

30436

40582

50727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7272

14544

21816

29088

36360

<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:

0.156

AC:

23676

AN:

152184

Hom.:

2232

Cov.:

AF XY:

0.155

AC XY:

11566

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0510

AC:

2117

AN:

41550

American (AMR)

AF:

0.257

AC:

3930

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

681

AN:

3466

East Asian (EAS)

AF:

0.219

AC:

1132

AN:

5176

South Asian (SAS)

AF:

0.0750

AC:

362

AN:

4826

European-Finnish (FIN)

AF:

0.183

AC:

1941

AN:

10602

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.189

AC:

12846

AN:

67982

Other (OTH)

AF:

0.193

AC:

407

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1006

2012

3017

4023

5029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.174

Hom.:

8525

Bravo

AF:

0.158

Asia WGS

AF:

0.155

AC:

542

AN:

3478

EpiCase

AF:

0.180

EpiControl

AF:

0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.7

(source)

DANN

Benign

0.84

PhyloP100

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over