chr1-46665281-T-G

Variant names:

• chr1-46665281-T-G
• NM_001394565.1:c.350A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394565.1(ATPAF1):​c.350A>C​(p.Asp117Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATPAF1 NM_001394565.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34744278).

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.350A>C	p.Asp117Ala	missense	Exon 2 of 9	NP_001381494.1	Q5TC12-1
	ATPAF1	NM_022745.6		c.419A>C	p.Asp140Ala	missense	Exon 2 of 9	NP_073582.3	I3L448
	ATPAF1	NM_001042546.2		c.419A>C	p.Asp140Ala	missense	Exon 2 of 7	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.350A>C	p.Asp117Ala	missense	Exon 2 of 9	ENSP00000459167.2	Q5TC12-1
	ATPAF1	ENST00000576409.5	TSL:1	c.419A>C	p.Asp140Ala	missense	Exon 2 of 9	ENSP00000460964.1	I3L448
	ATPAF1	ENST00000870207.1		c.350A>C	p.Asp117Ala	missense	Exon 2 of 9	ENSP00000540266.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.14
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.022
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.034	D
Polyphen		0.97	D
Vest4		0.33
MutPred		0.58		Gain of catalytic residue at D117 (P = 0.0399)
MVP		0.43
MPC		0.73
ClinPred		0.88	D
GERP RS		5.9
PromoterAI		-0.012	Neutral
Varity_R		0.24
gMVP		0.29
Mutation Taster		=177/123	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: chr1-47130953;