Variant chr1-46668330-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000576409.5(ATPAF1):c.62G>C(p.Gly21Ala) variant causes a missense 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
ENST00000576409.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00900

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 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/exons	MANE	Protein
ATPAF1	NM_001394565.1 linkuse as main transcript	c.-8G>C		5_prime_UTR_variant	1/9	ENST00000574428.6	NP_001381494.1
ATPAF1	NM_022745.6 linkuse as main transcript	c.62G>C	p.Gly21Ala	missense_variant	1/9		NP_073582.3
ATPAF1	NM_001042546.2 linkuse as main transcript	c.62G>C	p.Gly21Ala	missense_variant	1/7		NP_001036011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATPAF1	ENST00000576409.5 linkuse as main transcript	c.62G>C	p.Gly21Ala	missense_variant	1/9	1		ENSP00000460964	P1
ATPAF1	ENST00000574428.6 linkuse as main transcript	c.-8G>C		5_prime_UTR_variant	1/9	1	NM_001394565.1	ENSP00000459167		Q5TC12-1
ATPAF1	ENST00000329231.8 linkuse as main transcript	c.62G>C	p.Gly21Ala	missense_variant	1/7	2		ENSP00000330685
ATPAF1	ENST00000525633.1 linkuse as main transcript	n.315-2966G>C		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:

1207218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

591466

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

Jun 23, 2023

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

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

MutationTaster

Benign

1.0

D;D;N;N;D

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

gMVP

0.37

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