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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005001.5. 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
	NDUFA7	NM_005001.5	MANE Select	c.300C>T	p.Pro100Pro	synonymous	Exon 4 of 4	NP_004992.2	O95182
	NDUFA7	NR_135539.2		n.317C>T		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFA7	ENST00000301457.3	TSL:1 MANE Select	c.300C>T	p.Pro100Pro	synonymous	Exon 4 of 4	ENSP00000301457.1	O95182
ENSG00000167774	ENST00000598884.1	TSL:4	n.300C>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000470609.1
NDUFA7	ENST00000930188.1		c.393C>T	p.Pro131Pro	synonymous	Exon 5 of 5	ENSP00000600247.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over