Genetic Variant ATPAF1:p.Thr293Thr (chr1-46635884-G-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001394565.1(ATPAF1):c.879C>G(p.Thr293Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,614,248 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 13 hom. )

Consequence

ATPAF1
NM_001394565.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.163

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.033).

BP6

Variant 1-46635884-G-C is Benign according to our data. Variant chr1-46635884-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3024987.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.163 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATPAF1	NM_001394565.1 link	c.879C>G	p.Thr293Thr	synonymous_variant	Exon 9 of 9	ENST00000574428.6	NP_001381494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATPAF1	ENST00000574428.6 link	c.879C>G	p.Thr293Thr	synonymous_variant	Exon 9 of 9	1	NM_001394565.1	ENSP00000459167.2		Q5TC12-1

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

317

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00347

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00181

AC:

454

AN:

251464

AF XY:

0.00188

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00115

Gnomad NFE exome

AF:

0.00289

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00253

AC:

3700

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

1816

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000418

AC:

AN:

33480

American (AMR)

AF:

0.00127

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00187

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00187

AC:

100

AN:

53418

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00300

AC:

3339

AN:

1112006

Other (OTH)

AF:

0.00217

AC:

131

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

217

435

652

870

1087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00208

AC:

317

AN:

152362

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

158

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.000673

AC:

AN:

41580

American (AMR)

AF:

0.00163

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000847

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00347

AC:

236

AN:

68038

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00224

Hom.:

Bravo

AF:

0.00202

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00365

EpiControl

AF:

0.00290

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ATPAF1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.5

(source)

DANN

Benign

0.55

PhyloP100

0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=92/8

polymorphism

(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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chr1-46635884-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over