dbSNP rs1378161854: ATPAF1:p.Arg79Cys (chr1-46668088-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394565.1(ATPAF1):c.235C>T(p.Arg79Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000614 in 1,302,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000061 ( 0 hom. )

Consequence

ATPAF1
NM_001394565.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATPAF1	NM_001394565.1 link	c.235C>T	p.Arg79Cys	missense_variant	Exon 1 of 9	ENST00000574428.6	NP_001381494.1
ATPAF1	NM_022745.6 link	c.304C>T	p.Arg102Cys	missense_variant	Exon 1 of 9		NP_073582.3	Q5TC12I3L448
ATPAF1	NM_001042546.2 link	c.304C>T	p.Arg102Cys	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.235C>T	p.Arg79Cys	missense_variant	Exon 1 of 9	1	NM_001394565.1	ENSP00000459167.2		Q5TC12-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000614

AC:

AN:

1302054

Hom.:

Cov.:

AF XY:

0.00000312

AC XY:

AN XY:

641368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26300

American (AMR)

AF:

0.00

AC:

AN:

22892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22462

East Asian (EAS)

AF:

0.00

AC:

AN:

27854

South Asian (SAS)

AF:

0.0000147

AC:

AN:

68126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3826

European-Non Finnish (NFE)

AF:

0.00000677

AC:

AN:

1033492

Other (OTH)

AF:

0.00

AC:

AN:

53272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.304C>T (p.R102C) 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 304, causing the arginine (R) at amino acid position 102 to be replaced by a cysteine (C). 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

0.39

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.95

.;D;D;D

M_CAP

Pathogenic

0.89

MetaRNN

Uncertain

0.51

D;D;D;D

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.90

.;.;L;.

PhyloP100

1.7

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.3

.;D;.;D

REVEL

Uncertain

0.34

Sift

Benign

0.048

.;D;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.28

MutPred

0.70

.;.;Loss of MoRF binding (P = 0.0079);.;

MVP

0.57

MPC

1.5

ClinPred

0.99

GERP RS

4.3

PromoterAI

-0.055

Neutral

(source)

Varity_R

0.72

gMVP

0.40

Mutation Taster

=66/34

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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rs1378161854

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over