Variant 1-46668230-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001394565.1(ATPAF1):c.93C>A(p.Ser31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000082 in 1,219,124 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 8.2e-7 ( 0 hom. )

Consequence

ATPAF1
NM_001394565.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.847

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35154456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATPAF1	NM_001394565.1 linkuse as main transcript	c.93C>A	p.Ser31Arg	missense_variant	1/9	ENST00000574428.6	NP_001381494.1
ATPAF1	NM_022745.6 linkuse as main transcript	c.162C>A	p.Ser54Arg	missense_variant	1/9		NP_073582.3
ATPAF1	NM_001042546.2 linkuse as main transcript	c.162C>A	p.Ser54Arg	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.93C>A	p.Ser31Arg	missense_variant	1/9	1	NM_001394565.1	ENSP00000459167		Q5TC12-1
ATPAF1	ENST00000576409.5 linkuse as main transcript	c.162C>A	p.Ser54Arg	missense_variant	1/9	1		ENSP00000460964	P1
ATPAF1	ENST00000329231.8 linkuse as main transcript	c.162C>A	p.Ser54Arg	missense_variant	1/7	2		ENSP00000330685
ATPAF1	ENST00000525633.1 linkuse as main transcript	n.315-2866C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.20e-7

AC:

AN:

1219124

Hom.:

Cov.:

AF XY:

0.00000168

AC XY:

AN XY:

595270

show subpopulations

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:

0.0000331

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

Dec 15, 2022

The c.162C>A (p.S54R) alteration is located in exon 1 (coding exon 1) of the ATPAF1 gene. This alteration results from a C to A substitution at nucleotide position 162, causing the serine (S) at amino acid position 54 to be replaced by an arginine (R). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;T;T;T

Eigen

Benign

-0.054

Eigen_PC

Benign

0.020

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.74

.;T;T;T

M_CAP

Pathogenic

0.89

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;.;L;.

MutationTaster

Benign

0.65

D;D;D;D;D

PrimateAI

Pathogenic

0.95

REVEL

Benign

0.20

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.65

.;.;P;.

Vest4

0.35

MutPred

0.38

.;.;Loss of catalytic residue at S31 (P = 0.004);.;

MVP

0.45

MPC

0.53

ClinPred

0.92

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.48

gMVP

0.53

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