1-46652517-G-T

Position:

• chr1-46652517-G-T

Variant summary

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

The ENST00000574428.6(ATPAF1):​c.588+64C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,444,534 control chromosomes in the GnomAD database, including 83,239 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 0.40 (14170 hom., cov: 32)
  • Exomes 𝑓: 0.29 (69069 hom.)
• Consequence: ATPAF1 ENST00000574428.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173

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 = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATPAF1	NM_001394565.1	c.588+64C>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+64C>A		intron_variant		1	NM_001394565.1	ENSP00000459167

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61002 AN: 151756 Hom.: 14101 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.292 AC: 377720 AN: 1292660 Hom.: 69069 Cov.: 21 AF XY: 0.294 AC XY: 190492 AN XY: 648462

Gnomad4 AFR exome AF: 0.609

Gnomad4 AMR exome AF: 0.459

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.784

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.403 AC: 61137 AN: 151874 Hom.: 14170 Cov.: 32 AF XY: 0.409 AC XY: 30354 AN XY: 74254

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.418

Alfa AF: 0.170 Hom.: 293

Bravo AF: 0.423

Asia WGS AF: 0.601 AC: 2074 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.67

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: rs620431; hg19: chr1-47118189;