1-111456094-G-T

Variant names:

• chr1-111456094-G-T
• rs61752545
• NM_001688.5:c.232G>T

Variant summary

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

The NM_001688.5(ATP5PB):​c.232G>T​(p.Val78Leu) 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. V78I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP5PB NM_001688.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13853788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5PB	NM_001688.5	c.232G>T	p.Val78Leu	missense_variant	Exon 4 of 7	ENST00000369722.8	NP_001679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5PB	ENST00000369722.8	c.232G>T	p.Val78Leu	missense_variant	Exon 4 of 7	1	NM_001688.5	ENSP00000358737.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 231454 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;.
PhyloP100		1.5
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.097
Sift	Benign	0.15	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.049	B;.
Vest4		0.33
MutPred		0.41		Gain of helix (P = 0.132);.;
MVP		0.15
MPC		0.20
ClinPred		0.29	T
GERP RS		0.45
Varity_R		0.17
gMVP		0.61
Mutation Taster		=80/20	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: rs61752545; hg19: chr1-111998716; COSMIC: COSV100867612;