dbSNP rs782318204: PHB2:p.Glu229Gln (chr12-6967702-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144831.2(PHB2):c.685G>C(p.Glu229Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PHB2
NM_001144831.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.00

Variant links:

Genes affected

PHB2 (HGNC:30306): (prohibitin 2) Enables several functions, including protein C-terminus binding activity; protein N-terminus binding activity; and protein dimerization activity. Involved in several processes, including defense response to virus; positive regulation of cell cycle phase transition; and regulation of transcription, DNA-templated. Located in several cellular components, including cell surface; mitochondrial membrane; and nuclear matrix. Part of mitochondrial prohibitin complex. [provided by Alliance of Genome Resources, Apr 2022]

PHB2 links:

SCARNA12 (HGNC:32569): (small Cajal body-specific RNA 12) This gene produces a small nuclear RNA that localizes specifically to Cajal bodies, which are conserved subnuclear organelles that are present in the nucleoplasm. This RNA is processed from an intron of the prohibitin 2 host gene. It includes both an H/ACA box and a C/D box, and is thought to guide the pseudouridylation of residue U46 in the U5 small nuclear RNA. [provided by RefSeq, Jun 2010]

SCARNA12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHB2	NM_001144831.2 link	c.685G>C	p.Glu229Gln	missense_variant	Exon 6 of 10	ENST00000535923.6	NP_001138303.1	Q99623-1
PHB2	NM_001267700.1 link	c.607+190G>C		intron_variant	Intron 5 of 8		NP_001254629.1	Q99623-2
PHB2	XM_047428234.1 link	c.607+190G>C		intron_variant	Intron 5 of 5		XP_047284190.1
SCARNA12	NR_003010.1 link	n.-96G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHB2	ENST00000535923.6 link	c.685G>C	p.Glu229Gln	missense_variant	Exon 6 of 10	5	NM_001144831.2	ENSP00000441875.1		Q99623-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461510

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Benign

0.84

DEOGEN2

Benign

0.31

T;T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.7

L;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.57

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.95

P;.;.

Vest4

0.73

MutPred

0.41

Gain of MoRF binding (P = 0.0307);Gain of MoRF binding (P = 0.0307);Gain of MoRF binding (P = 0.0307);

MVP

0.55

MPC

1.7

ClinPred

0.96

GERP RS

3.7

Varity_R

0.48

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over