1-46668259-G-A

Position:

• chr1-46668259-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394565.1(ATPAF1):​c.64C>T​(p.Leu22Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 NM_001394565.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATPAF1	NM_001394565.1	c.64C>T	p.Leu22Phe	missense_variant	1/9	ENST00000574428.6
ATPAF1	NM_022745.6	c.133C>T	p.Leu45Phe	missense_variant	1/9
ATPAF1	NM_001042546.2	c.133C>T	p.Leu45Phe	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATPAF1	ENST00000574428.6	c.64C>T	p.Leu22Phe	missense_variant	1/9	1	NM_001394565.1
ATPAF1	ENST00000576409.5	c.133C>T	p.Leu45Phe	missense_variant	1/9	1		P1
ATPAF1	ENST00000329231.8	c.133C>T	p.Leu45Phe	missense_variant	1/7	2
ATPAF1	ENST00000525633.1	n.315-2895C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1239872 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 608172

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.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.133C>T (p.L45F) 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 133, causing the leucine (L) at amino acid position 45 to be replaced by a phenylalanine (F). 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	Benign	0.14
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T;T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.74	.;T;T;T
M_CAP	Pathogenic	0.92	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	2.0	.;.;M;.
MutationTaster	Benign	0.70	D;D;D;D;D
PrimateAI	Pathogenic	0.94	D
REVEL	Benign	0.10
Sift4G	Benign	0.062	T;T;T;T
Polyphen		0.99	.;.;D;.
Vest4		0.30
MutPred		0.22		.;.;Loss of MoRF binding (P = 0.1135);.;
MVP		0.69
MPC		1.3
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.40

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.

Other links and lift over

hg19: chr1-47133931;