rs654509

Variant names:

• chr1-46661499-G-A
• rs654509
• NM_001394565.1:c.376-2762C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001394565.1(ATPAF1):​c.376-2762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 152,280 control chromosomes in the GnomAD database, including 48 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 0.014 (48 hom., cov: 32)
• Consequence: ATPAF1 NM_001394565.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 2 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=-0.96).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0137 (2081/152280) while in subpopulation AFR AF = 0.0476 (1978/41550). AF 95% confidence interval is 0.0459. There are 48 homozygotes in GnomAd4. There are 1012 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394565.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATPAF1	NM_001394565.1	MANE Select	c.376-2762C>T		intron	N/A	NP_001381494.1	Q5TC12-1
	ATPAF1	NM_022745.6		c.445-2762C>T		intron	N/A	NP_073582.3	I3L448
	ATPAF1	NM_001042546.2		c.445-2762C>T		intron	N/A	NP_001036011.2	Q5TC12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATPAF1	ENST00000574428.6	TSL:1 MANE Select	c.376-2762C>T		intron	N/A	ENSP00000459167.2	Q5TC12-1
	ATPAF1	ENST00000576409.5	TSL:1	c.445-2762C>T		intron	N/A	ENSP00000460964.1	I3L448
	ATPAF1	ENST00000870207.1		c.376-2735C>T		intron	N/A	ENSP00000540266.1

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2053 AN: 152162 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00861

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0137 AC: 2081 AN: 152280 Hom.: 48 Cov.: 32 AF XY: 0.0136 AC XY: 1012 AN XY: 74458

African (AFR) AF: 0.0476 AC: 1978 AN: 41550

American (AMR) AF: 0.00360 AC: 55 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68018

Other (OTH) AF: 0.00852 AC: 18 AN: 2112

Alfa AF: 0.0136 Hom.: 3

Bravo AF: 0.0152

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.40
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

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: rs654509; hg19: chr1-47127171;