chr1-46668259-G-C

Variant names:

• chr1-46668259-G-C
• rs1244209138
• NM_001394565.1:c.64C>G

Variant summary

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

The NM_001394565.1(ATPAF1):​c.64C>G​(p.Leu22Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000664 in 150,572 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. L22F) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: ATPAF1 NM_001394565.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• Publications: 0 publications found

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]

ACMG classification

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	c.64C>G	p.Leu22Val	missense_variant	Exon 1 of 9	ENST00000574428.6	NP_001381494.1
ATPAF1	NM_022745.6	c.133C>G	p.Leu45Val	missense_variant	Exon 1 of 9		NP_073582.3
ATPAF1	NM_001042546.2	c.133C>G	p.Leu45Val	missense_variant	Exon 1 of 7		NP_001036011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATPAF1	ENST00000574428.6	c.64C>G	p.Leu22Val	missense_variant	Exon 1 of 9	1	NM_001394565.1	ENSP00000459167.2

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150572 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

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

GnomAD4 exome Cov.: 35

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150572 Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1 AN XY: 73494

African (AFR) AF: 0.00 AC: 0 AN: 41078

American (AMR) AF: 0.00 AC: 0 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5052

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67502

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T;T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.73	.;T;T;T
M_CAP	Pathogenic	0.90	D
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	2.0	.;.;M;.
PhyloP100		4.0
PrimateAI	Pathogenic	0.93	D
REVEL	Benign	0.055
Sift4G	Benign	0.085	T;T;T;T
Polyphen		0.77	.;.;P;.
Vest4		0.29
MutPred		0.26		.;.;Loss of helix (P = 0.0068);.;
MVP		0.65
MPC		1.1
ClinPred		0.94	D
GERP RS		4.8
PromoterAI		-0.065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.45
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs1244209138; hg19: chr1-47133931;