Variant 1-46668259-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394565.1(ATPAF1):c.64C>T(p.Leu22Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATPAF1	NM_001394565.1 linkuse as main transcript	c.64C>T	p.Leu22Phe	missense_variant	1/9	ENST00000574428.6	NP_001381494.1
ATPAF1	NM_022745.6 linkuse as main transcript	c.133C>T	p.Leu45Phe	missense_variant	1/9		NP_073582.3
ATPAF1	NM_001042546.2 linkuse as main transcript	c.133C>T	p.Leu45Phe	missense_variant	1/7		NP_001036011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATPAF1	ENST00000574428.6 linkuse as main transcript	c.64C>T	p.Leu22Phe	missense_variant	1/9	1	NM_001394565.1	ENSP00000459167		Q5TC12-1
ATPAF1	ENST00000576409.5 linkuse as main transcript	c.133C>T	p.Leu45Phe	missense_variant	1/9	1		ENSP00000460964	P1
ATPAF1	ENST00000329231.8 linkuse as main transcript	c.133C>T	p.Leu45Phe	missense_variant	1/7	2		ENSP00000330685
ATPAF1	ENST00000525633.1 linkuse as main transcript	n.315-2895C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1239872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

608172

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.133C>T (p.L45F) alteration is located in exon 1 (coding exon 1) of the ATPAF1 gene. This alteration results from a C to T substitution at nucleotide position 133, causing the leucine (L) at amino acid position 45 to be replaced by a phenylalanine (F). 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

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

T;T;T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.74

.;T;T;T

M_CAP

Pathogenic

0.92

MetaRNN

Uncertain

0.52

D;D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Benign

2.0

.;.;M;.

MutationTaster

Benign

0.70

D;D;D;D;D

PrimateAI

Pathogenic

0.94

REVEL

Benign

0.10

Sift4G

Benign

0.062

T;T;T;T

Polyphen

0.99

.;.;D;.

Vest4

0.30

MutPred

0.22

.;.;Loss of MoRF binding (P = 0.1135);.;

MVP

0.69

MPC

1.3

ClinPred

0.95

GERP RS

4.8

Varity_R

0.18

gMVP

0.40

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over