Genetic Variant NM_001394565.1:c.235C>G (chr1-46668088-G-C) – 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>G(p.Arg79Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,936 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R79C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

ATPAF1
NM_001394565.1 missense

Scores

Clinical Significance

Not reported in ClinVar

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>G	p.Arg79Gly	missense_variant	Exon 1 of 9	ENST00000574428.6	NP_001381494.1
ATPAF1	NM_022745.6 link	c.304C>G	p.Arg102Gly	missense_variant	Exon 1 of 9		NP_073582.3	Q5TC12I3L448
ATPAF1	NM_001042546.2 link	c.304C>G	p.Arg102Gly	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>G	p.Arg79Gly	missense_variant	Exon 1 of 9	1	NM_001394565.1	ENSP00000459167.2		Q5TC12-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000133

AC:

AN:

75330

AF XY:

0.0000232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000814

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000154

AC:

AN:

1302054

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

641368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26300

American (AMR)

AF:

0.0000874

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:

0.00

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:

0.00

AC:

AN:

1033492

Other (OTH)

AF:

0.00

AC:

AN:

53272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151882

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41390

American (AMR)

AF:

0.000131

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67902

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T;T;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.90

.;D;D;D

M_CAP

Pathogenic

0.74

MetaRNN

Uncertain

0.51

D;D;D;D

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

.;.;L;.

PhyloP100

1.7

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.3

.;D;.;D

REVEL

Benign

0.17

Sift

Benign

0.17

.;T;.;D

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

0.65

.;.;P;.

Vest4

0.33

MutPred

0.69

.;.;Loss of helix (P = 0.0167);.;

MVP

0.53

MPC

1.2

ClinPred

0.95

GERP RS

4.3

PromoterAI

0.016

Neutral

(source)

Varity_R

0.72

gMVP

0.37

Mutation Taster

=67/33

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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NM_001394565.1:c.235C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over