1-46652496-C-T

Position:

• chr1-46652496-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+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,303,062 control chromosomes in the GnomAD database, including 38,026 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 0.22 (3896 hom., cov: 32)
  • Exomes 𝑓: 0.23 (34130 hom.)
• Consequence: ATPAF1 NM_001394565.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.06

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATPAF1	NM_001394565.1	c.588+85G>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+85G>A		intron_variant		1	NM_001394565.1	ENSP00000459167

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32724 AN: 151884 Hom.: 3892 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.230 AC: 264963 AN: 1151060 Hom.: 34130 Cov.: 15 AF XY: 0.230 AC XY: 133747 AN XY: 582058

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.215 AC: 32746 AN: 152002 Hom.: 3896 Cov.: 32 AF XY: 0.217 AC XY: 16105 AN XY: 74280

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.254

Alfa AF: 0.199 Hom.: 1036

Bravo AF: 0.215

Asia WGS AF: 0.158 AC: 548 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.74

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: rs2289447; hg19: chr1-47118168;