12-56645315-C-A

Variant names:

• chr12-56645315-C-A
• rs901967218
• NM_001686.4:c.166G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001686.4(ATP5F1B):​c.166G>T​(p.Ala56Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. A56T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP5F1B NM_001686.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 0 publications found

Genes affected

ATP5F1B (HGNC:830): (ATP synthase F1 subunit beta) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the beta subunit of the catalytic core. [provided by RefSeq, Jul 2008]

SNORD59A (HGNC:10210): (small nucleolar RNA, C/D box 59A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12709358).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001686.4. 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
	ATP5F1B	NM_001686.4	MANE Select	c.166G>T	p.Ala56Ser	missense	Exon 2 of 10	NP_001677.2
	SNORD59A	NR_002737.1		n.-214G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5F1B	ENST00000262030.8	TSL:1 MANE Select	c.166G>T	p.Ala56Ser	missense	Exon 2 of 10	ENSP00000262030.3	P06576
	ATP5F1B	ENST00000904666.1		c.166G>T	p.Ala56Ser	missense	Exon 2 of 11	ENSP00000574725.1
	ATP5F1B	ENST00000904670.1		c.193G>T	p.Ala65Ser	missense	Exon 2 of 10	ENSP00000574729.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.088
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.11
Sift	Benign	0.037	D
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.048
MutPred		0.23		Gain of glycosylation at A56 (P = 0.0016)
MVP		0.61
MPC		1.1
ClinPred		0.25	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.086
gMVP		0.29
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs901967218; hg19: chr12-57039099;