1-46652272-C-T

Position:

• chr1-46652272-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394565.1(ATPAF1):​c.588+309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 237,966 control chromosomes in the GnomAD database, including 4,500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (3807 hom., cov: 31)
  • Exomes 𝑓: 0.048 (693 hom.)
• Consequence: ATPAF1 NM_001394565.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATPAF1	NM_001394565.1	c.588+309G>A		intron_variant		ENST00000574428.6	NP_001381494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATPAF1	ENST00000574428.6	c.588+309G>A		intron_variant		1	NM_001394565.1	ENSP00000459167.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21126 AN: 151112 Hom.: 3786 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0419

Gnomad NFE AF: 0.00540

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.0476 AC: 4132 AN: 86760 Hom.: 693 AF XY: 0.0445 AC XY: 1954 AN XY: 43948

Gnomad4 AFR exome AF: 0.363

Gnomad4 AMR exome AF: 0.0547

Gnomad4 ASJ exome AF: 0.00857

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0180

Gnomad4 NFE exome AF: 0.00368

Gnomad4 OTH exome AF: 0.0549

GnomAD4 genome AF: 0.140 AC: 21204 AN: 151206 Hom.: 3807 Cov.: 31 AF XY: 0.143 AC XY: 10576 AN XY: 73816

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.0722

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.00539

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0507 Hom.: 439

Bravo AF: 0.153

Asia WGS AF: 0.298 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.7
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs631840; hg19: chr1-47117944;