chr1-46668376-C-A

Variant names:

• chr1-46668376-C-A
• ENST00000576409.5:c.16G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022745.6(ATPAF1):​c.16G>T​(p.Gly6Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000018 in 1,108,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ATPAF1 NM_022745.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022745.6. 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_022745.6		c.16G>T	p.Gly6Trp	missense	Exon 1 of 9	NP_073582.3	I3L448
	ATPAF1	NM_001042546.2		c.16G>T	p.Gly6Trp	missense	Exon 1 of 7	NP_001036011.2	Q5TC12
	ATPAF1	NM_001394565.1	MANE Select	c.-54G>T		upstream_gene	N/A	NP_001381494.1	Q5TC12-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATPAF1	ENST00000576409.5	TSL:1	c.16G>T	p.Gly6Trp	missense	Exon 1 of 9	ENSP00000460964.1	I3L448
	ATPAF1	ENST00000870203.1		c.-54G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000540262.1
	ATPAF1	ENST00000923240.1		c.-54G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000593299.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000180 AC: 2 AN: 1108256 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 535022

African (AFR) AF: 0.00 AC: 0 AN: 22136

American (AMR) AF: 0.00 AC: 0 AN: 9634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13692

East Asian (EAS) AF: 0.00 AC: 0 AN: 23272

South Asian (SAS) AF: 0.00 AC: 0 AN: 34202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2882

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 935728

Other (OTH) AF: 0.0000231 AC: 1 AN: 43298

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	0.0057	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0097	T
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Uncertain	0.48	T
PhyloP100		2.4
PrimateAI	Pathogenic	0.82	D
Sift4G	Pathogenic	0.0	D
Vest4		0.41
MVP		0.87
MPC		0.53
GERP RS		3.8
PromoterAI		-0.11	Neutral
gMVP		0.35
Mutation Taster		=281/19	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

hg19: chr1-47134048;