Genetic Variant ATPAF1:c.588+85G>A (chr1-46652496-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001394565.1(ATPAF1):c.588+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,303,062 control chromosomes in the GnomAD database, including 38,026 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 ( 3896 hom., cov: 32)

Exomes 𝑓: 0.23 ( 34130 hom. )

Consequence

ATPAF1
NM_001394565.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.06

Publications

9 publications found

Variant links:

Genes affected

ATPAF1 (HGNC:18803): (ATP synthase mitochondrial F1 complex assembly factor 1) This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 beta subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Aug 2011]

ATPAF1 links:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394565.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATPAF1	NM_001394565.1	MANE Select	c.588+85G>A	intron	N/A	NP_001381494.1	Q5TC12-1
ATPAF1	NM_022745.6		c.657+85G>A	intron	N/A	NP_073582.3	I3L448
ATPAF1	NM_001042546.2		c.657+85G>A	intron	N/A	NP_001036011.2	Q5TC12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATPAF1	ENST00000574428.6	TSL:1 MANE Select	c.588+85G>A	intron	N/A	ENSP00000459167.2	Q5TC12-1
ATPAF1	ENST00000576409.5	TSL:1	c.657+85G>A	intron	N/A	ENSP00000460964.1	I3L448
ATPAF1	ENST00000870207.1		c.615+85G>A	intron	N/A	ENSP00000540266.1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32724

AN:

151884

Hom.:

3892

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.230

AC:

264963

AN:

1151060

Hom.:

34130

Cov.:

AF XY:

0.230

AC XY:

133747

AN XY:

582058

show subpopulations

African (AFR)

AF:

0.107

AC:

2824

AN:

26354

American (AMR)

AF:

0.266

AC:

10263

AN:

38548

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

7186

AN:

22822

East Asian (EAS)

AF:

0.165

AC:

6013

AN:

36470

South Asian (SAS)

AF:

0.178

AC:

13346

AN:

74852

European-Finnish (FIN)

AF:

0.238

AC:

12240

AN:

51362

Middle Eastern (MID)

AF:

0.288

AC:

1465

AN:

5090

European-Non Finnish (NFE)

AF:

0.236

AC:

199931

AN:

845966

Other (OTH)

AF:

0.236

AC:

11695

AN:

49596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

9280

18561

27841

37122

46402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5876

11752

17628

23504

29380

<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:

0.215

AC:

32746

AN:

152002

Hom.:

3896

Cov.:

AF XY:

0.217

AC XY:

16105

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.117

AC:

4871

AN:

41478

American (AMR)

AF:

0.297

AC:

4541

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

1155

AN:

3468

East Asian (EAS)

AF:

0.164

AC:

851

AN:

5174

South Asian (SAS)

AF:

0.183

AC:

881

AN:

4820

European-Finnish (FIN)

AF:

0.236

AC:

2490

AN:

10538

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.252

AC:

17145

AN:

67946

Other (OTH)

AF:

0.254

AC:

535

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1305

2611

3916

5222

6527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.205

Hom.:

1376

Bravo

AF:

0.215

Asia WGS

AF:

0.158

AC:

548

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.18

(source)

DANN

Benign

0.74

PhyloP100

-4.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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