1-46652517-G-T

Variant names:

• chr1-46652517-G-T
• rs620431
• NM_001394565.1:c.588+64C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394565.1(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 NM_001394565.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ATPAF1	NM_001394565.1	c.588+64C>A		intron_variant	Intron 6 of 8	ENST00000574428.6	NP_001381494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATPAF1	ENST00000574428.6	c.588+64C>A		intron_variant	Intron 6 of 8	1	NM_001394565.1	ENSP00000459167.2

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

African (AFR) AF: 0.609 AC: 18299 AN: 30038

American (AMR) AF: 0.459 AC: 19167 AN: 41764

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 8382 AN: 24298

East Asian (EAS) AF: 0.784 AC: 30128 AN: 38450

South Asian (SAS) AF: 0.377 AC: 30446 AN: 80856

European-Finnish (FIN) AF: 0.283 AC: 14837 AN: 52428

Middle Eastern (MID) AF: 0.361 AC: 1961 AN: 5430

European-Non Finnish (NFE) AF: 0.245 AC: 235895 AN: 964690

Other (OTH) AF: 0.340 AC: 18605 AN: 54706

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

African (AFR) AF: 0.591 AC: 24477 AN: 41398

American (AMR) AF: 0.453 AC: 6913 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1254 AN: 3464

East Asian (EAS) AF: 0.779 AC: 4022 AN: 5164

South Asian (SAS) AF: 0.409 AC: 1968 AN: 4812

European-Finnish (FIN) AF: 0.294 AC: 3097 AN: 10542

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18203 AN: 67928

Other (OTH) AF: 0.418 AC: 880 AN: 2106

Alfa AF: 0.195 Hom.: 421

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
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs620431; hg19: chr1-47118189;