Genetic Variant ATPAF1:p.Gly21Ala (chr1-46668330-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394565.1(ATPAF1):c.-8G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATPAF1
NM_001394565.1 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00900

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11410743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATPAF1	NM_001394565.1 link	c.-8G>C		5_prime_UTR_variant	Exon 1 of 9	ENST00000574428.6	NP_001381494.1
ATPAF1	NM_022745.6 link	c.62G>C	p.Gly21Ala	missense_variant	Exon 1 of 9		NP_073582.3	Q5TC12I3L448
ATPAF1	NM_001042546.2 link	c.62G>C	p.Gly21Ala	missense_variant	Exon 1 of 7		NP_001036011.2	Q5TC12A8MRA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATPAF1	ENST00000574428.6 link	c.-8G>C		5_prime_UTR_variant	Exon 1 of 9	1	NM_001394565.1	ENSP00000459167.2		Q5TC12-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1207218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

591466

African (AFR)

AF:

0.00

AC:

AN:

24668

American (AMR)

AF:

0.00

AC:

AN:

20374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18920

East Asian (EAS)

AF:

0.00

AC:

AN:

25122

South Asian (SAS)

AF:

0.00

AC:

AN:

54822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3350

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

983432

Other (OTH)

AF:

0.00

AC:

AN:

48084

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.62G>C (p.G21A) alteration is located in exon 1 (coding exon 1) of the ATPAF1 gene. This alteration results from a G to C substitution at nucleotide position 62, causing the glycine (G) at amino acid position 21 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.3

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.011

T;T;T

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.26

.;T;T

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.11

T;T;T

PhyloP100

-0.0090

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.49

.;N;N

Sift

Benign

1.0

.;T;T

Sift4G

Benign

0.60

T;T;T

Vest4

0.20

MVP

0.70

MPC

0.48

GERP RS

-0.65

PromoterAI

0.23

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

gMVP

0.37

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over