17-18021554-A-G

Position:

• chr17-18021554-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145691.4(ATPAF2):​c.616+191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 647,418 control chromosomes in the GnomAD database, including 65,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13474 hom., cov: 32)
  • Exomes 𝑓: 0.43 (52461 hom.)
• Consequence: ATPAF2 NM_145691.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.639

Genes affected

ATPAF2 (HGNC:18802): (ATP synthase mitochondrial F1 complex assembly factor 2) This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. This gene is located within the Smith-Magenis syndrome region on chromosome 17. An alternatively spliced transcript variant has been described, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-18021554-A-G is Benign according to our data. Variant chr17-18021554-A-G is described in ClinVar as [Benign]. Clinvar id is 669688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATPAF2	NM_145691.4	c.616+191T>C		intron_variant		ENST00000474627.8	NP_663729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATPAF2	ENST00000474627.8	c.616+191T>C		intron_variant		1	NM_145691.4	ENSP00000417190	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61173 AN: 151950 Hom.: 13467 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.427 AC: 211451 AN: 495350 Hom.: 52461 Cov.: 5 AF XY: 0.441 AC XY: 116559 AN XY: 264268

Gnomad4 AFR exome AF: 0.412

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.862

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.403 AC: 61214 AN: 152068 Hom.: 13474 Cov.: 32 AF XY: 0.416 AC XY: 30927 AN XY: 74340

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.405

Alfa AF: 0.384 Hom.: 2025

Bravo AF: 0.409

Asia WGS AF: 0.704 AC: 2447 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9896837; hg19: chr17-17924868;