1-46668376-C-A

Variant names:

• chr1-46668376-C-A
• ENST00000576409.5:c.16G>T

Variant summary

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

The NM_022745.6(ATPAF1):​c.16G>T​(p.Gly6Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000018 in 1,108,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ATPAF1 NM_022745.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

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 rank	MANE	Protein	UniProt
ATPAF1	NM_022745.6	c.16G>T	p.Gly6Trp	missense_variant	Exon 1 of 9		NP_073582.3
ATPAF1	NM_001042546.2	c.16G>T	p.Gly6Trp	missense_variant	Exon 1 of 7		NP_001036011.2
ATPAF1	NM_001394565.1	c.-54G>T		upstream_gene_variant		ENST00000574428.6	NP_001381494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATPAF1	ENST00000574428.6	c.-54G>T		upstream_gene_variant		1	NM_001394565.1	ENSP00000459167.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000180 AC: 2 AN: 1108256 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 535022

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: 0.00000107

Gnomad4 OTH exome AF: 0.0000231

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16G>T (p.G6W) alteration is located in exon 1 (coding exon 1) of the ATPAF1 gene. This alteration results from a G to T substitution at nucleotide position 16, causing the glycine (G) at amino acid position 6 to be replaced by a tryptophan (W). 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	0.0057	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0097	T;T;T
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.59	.;T;T
M_CAP	Pathogenic	0.92	D
MetaRNN	Uncertain	0.48	T;T;T
PrimateAI	Pathogenic	0.82	D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.41
MVP		0.87
MPC		0.53
GERP RS		3.8
gMVP		0.35

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: chr1-47134048;