1-111460927-C-T

Variant names:

• chr1-111460927-C-T
• rs1317681359
• NM_001688.5:c.704C>T

Variant summary

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

The NM_001688.5(ATP5PB):​c.704C>T​(p.Thr235Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,306 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. T235R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATP5PB NM_001688.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29
• Publications: 0 publications found

Genes affected

ATP5PB (HGNC:840): (ATP synthase peripheral stalk-membrane subunit b) 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 seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the b subunit of the proton channel. [provided by RefSeq, Jul 2008]

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=0.2940902).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001688.5. 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
	ATP5PB	NM_001688.5	MANE Select	c.704C>T	p.Thr235Ile	missense	Exon 7 of 7	NP_001679.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5PB	ENST00000369722.8	TSL:1 MANE Select	c.704C>T	p.Thr235Ile	missense	Exon 7 of 7	ENSP00000358737.3	P24539
	ATP5PB	ENST00000862240.1		c.740C>T	p.Thr247Ile	missense	Exon 7 of 7	ENSP00000532299.1
	ATP5PB	ENST00000862238.1		c.704C>T	p.Thr235Ile	missense	Exon 8 of 8	ENSP00000532297.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461306 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726958

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111720

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.18
Sift	Benign	0.064	T
Sift4G	Benign	0.070	T
Polyphen		0.54	P
Vest4		0.32
MutPred		0.52		Loss of helix (P = 0.0237)
MVP		0.27
MPC		0.59
ClinPred		0.96	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.35
Mutation Taster		=54/46	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: rs1317681359; hg19: chr1-112003549; COSMIC: COSV71953325; COSMIC: COSV71953325;