1-46652496-C-T

Variant names:

• chr1-46652496-C-T
• rs2289447
• NM_001394565.1:c.588+85G>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+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
• Publications: 9 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=-0.92).
• 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 rank	MANE	Protein	UniProt
ATPAF1	NM_001394565.1	c.588+85G>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+85G>A		intron_variant	Intron 6 of 8	1	NM_001394565.1	ENSP00000459167.2

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

African (AFR) AF: 0.107 AC: 2824 AN: 26354

American (AMR) AF: 0.266 AC: 10263 AN: 38548

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 7186 AN: 22822

East Asian (EAS) AF: 0.165 AC: 6013 AN: 36470

South Asian (SAS) AF: 0.178 AC: 13346 AN: 74852

European-Finnish (FIN) AF: 0.238 AC: 12240 AN: 51362

Middle Eastern (MID) AF: 0.288 AC: 1465 AN: 5090

European-Non Finnish (NFE) AF: 0.236 AC: 199931 AN: 845966

Other (OTH) AF: 0.236 AC: 11695 AN: 49596

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

African (AFR) AF: 0.117 AC: 4871 AN: 41478

American (AMR) AF: 0.297 AC: 4541 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3468

East Asian (EAS) AF: 0.164 AC: 851 AN: 5174

South Asian (SAS) AF: 0.183 AC: 881 AN: 4820

European-Finnish (FIN) AF: 0.236 AC: 2490 AN: 10538

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17145 AN: 67946

Other (OTH) AF: 0.254 AC: 535 AN: 2108

Alfa AF: 0.205 Hom.: 1376

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
PhyloP100		-4.1
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: rs2289447; hg19: chr1-47118168; COSMIC: COSV107338099; COSMIC: COSV107338099;