rs1273237

Variant names:

• chr1-46643579-A-G
• rs1273237
• NM_001394565.1:c.685-278T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001394565.1(ATPAF1):​c.685-278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,286 control chromosomes in the GnomAD database, including 60,291 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 0.88 (60291 hom., cov: 33)
• Consequence: ATPAF1 NM_001394565.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

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.685-278T>C		intron	N/A	NP_001381494.1	Q5TC12-1
	ATPAF1	NM_022745.6		c.754-278T>C		intron	N/A	NP_073582.3	I3L448
	ATPAF1	NM_001042546.2		c.658-7609T>C		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.685-278T>C		intron	N/A	ENSP00000459167.2	Q5TC12-1
	ATPAF1	ENST00000576409.5	TSL:1	c.754-278T>C		intron	N/A	ENSP00000460964.1	I3L448
	ATPAF1	ENST00000870207.1		c.712-278T>C		intron	N/A	ENSP00000540266.1

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133452 AN: 152168 Hom.: 60280 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.987

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.962

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.995

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.877 AC: 133514 AN: 152286 Hom.: 60291 Cov.: 33 AF XY: 0.873 AC XY: 65030 AN XY: 74452

African (AFR) AF: 0.663 AC: 27514 AN: 41522

American (AMR) AF: 0.934 AC: 14289 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.987 AC: 3424 AN: 3470

East Asian (EAS) AF: 0.604 AC: 3132 AN: 5182

South Asian (SAS) AF: 0.857 AC: 4138 AN: 4828

European-Finnish (FIN) AF: 0.962 AC: 10213 AN: 10614

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.995 AC: 67703 AN: 68044

Other (OTH) AF: 0.903 AC: 1908 AN: 2114

Alfa AF: 0.948 Hom.: 26931

Bravo AF: 0.866

Asia WGS AF: 0.706 AC: 2458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		2.7
Mutation Taster		=99/1	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: rs1273237; hg19: chr1-47109251;