Genetic Variant ATPAF1:c.588+309G>A (chr1-46652272-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+309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 237,966 control chromosomes in the GnomAD database, including 4,500 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 0.14 ( 3807 hom., cov: 31)

Exomes 𝑓: 0.048 ( 693 hom. )

Consequence

ATPAF1
NM_001394565.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.231

Publications

2 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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+309G>A	intron	N/A	NP_001381494.1	Q5TC12-1
ATPAF1	NM_022745.6		c.657+309G>A	intron	N/A	NP_073582.3	I3L448
ATPAF1	NM_001042546.2		c.657+309G>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+309G>A	intron	N/A	ENSP00000459167.2	Q5TC12-1
ATPAF1	ENST00000576409.5	TSL:1	c.657+309G>A	intron	N/A	ENSP00000460964.1	I3L448
ATPAF1	ENST00000870207.1		c.615+309G>A	intron	N/A	ENSP00000540266.1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21126

AN:

151112

Hom.:

3786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.396

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0722

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.0419

Gnomad NFE

AF:

0.00540

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.0476

AC:

4132

AN:

86760

Hom.:

693

AF XY:

0.0445

AC XY:

1954

AN XY:

43948

show subpopulations

African (AFR)

AF:

0.363

AC:

1014

AN:

2796

American (AMR)

AF:

0.0547

AC:

188

AN:

3434

Ashkenazi Jewish (ASJ)

AF:

0.00857

AC:

AN:

3736

East Asian (EAS)

AF:

0.332

AC:

2105

AN:

6332

South Asian (SAS)

AF:

0.103

AC:

150

AN:

1462

European-Finnish (FIN)

AF:

0.0180

AC:

AN:

4934

Middle Eastern (MID)

AF:

0.0222

AC:

AN:

450

European-Non Finnish (NFE)

AF:

0.00368

AC:

212

AN:

57574

Other (OTH)

AF:

0.0549

AC:

332

AN:

6042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

145

290

434

579

724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.140

AC:

21204

AN:

151206

Hom.:

3807

Cov.:

AF XY:

0.143

AC XY:

10576

AN XY:

73816

show subpopulations

African (AFR)

AF:

0.397

AC:

16308

AN:

41128

American (AMR)

AF:

0.0722

AC:

1099

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3466

East Asian (EAS)

AF:

0.397

AC:

2044

AN:

5152

South Asian (SAS)

AF:

0.143

AC:

681

AN:

4746

European-Finnish (FIN)

AF:

0.0386

AC:

397

AN:

10288

Middle Eastern (MID)

AF:

0.0455

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00539

AC:

366

AN:

67902

Other (OTH)

AF:

0.117

AC:

246

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

655

1310

1966

2621

3276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<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:

0.0510

Hom.:

514

Bravo

AF:

0.153

Asia WGS

AF:

0.298

AC:

1034

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

6.7

(source)

DANN

Benign

0.64

PhyloP100

0.23

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