NM_001394565.1:c.92G>T

Variant names:

• chr1-46668231-C-A
• rs1453792927
• NM_001394565.1:c.92G>T

Variant summary

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

The NM_001394565.1(ATPAF1):​c.92G>T​(p.Ser31Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000164 in 1,219,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S31N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ATPAF1 NM_001394565.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94
• 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=0.3804294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATPAF1	NM_001394565.1	c.92G>T	p.Ser31Ile	missense_variant	Exon 1 of 9	ENST00000574428.6	NP_001381494.1
ATPAF1	NM_022745.6	c.161G>T	p.Ser54Ile	missense_variant	Exon 1 of 9		NP_073582.3
ATPAF1	NM_001042546.2	c.161G>T	p.Ser54Ile	missense_variant	Exon 1 of 7		NP_001036011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATPAF1	ENST00000574428.6	c.92G>T	p.Ser31Ile	missense_variant	Exon 1 of 9	1	NM_001394565.1	ENSP00000459167.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000164 AC: 2 AN: 1219690 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 595636

African (AFR) AF: 0.00 AC: 0 AN: 24722

American (AMR) AF: 0.00 AC: 0 AN: 17870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19510

East Asian (EAS) AF: 0.00 AC: 0 AN: 26248

South Asian (SAS) AF: 0.00 AC: 0 AN: 54840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3504

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 993316

Other (OTH) AF: 0.0000202 AC: 1 AN: 49450

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;T;T;T
Eigen	Benign	0.093
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.72	.;T;T;T
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	.;.;L;.
PhyloP100		3.9
PrimateAI	Pathogenic	0.95	D
REVEL	Benign	0.18
Sift4G	Benign	0.067	T;T;T;T
Polyphen		0.48	.;.;P;.
Vest4		0.47
MutPred		0.36		.;.;Loss of catalytic residue at S31 (P = 0.0051);.;
MVP		0.47
MPC		0.96
ClinPred		0.97	D
GERP RS		5.1
PromoterAI		-0.24	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.52
Mutation Taster		=83/17	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

dbSNP: rs1453792927; hg19: chr1-47133903;