12-6970429-A-G

Variant names:

• chr12-6970429-A-G
• rs1555151894
• NM_001144831.2:c.115T>C

Variant summary

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

The NM_001144831.2(PHB2):​c.115T>C​(p.Ser39Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHB2 NM_001144831.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144831.2. 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
	PHB2	NM_001144831.2	MANE Select	c.115T>C	p.Ser39Pro	missense	Exon 1 of 10	NP_001138303.1	Q99623-1
	PHB2	NM_001267700.1		c.115T>C	p.Ser39Pro	missense	Exon 1 of 9	NP_001254629.1	Q99623-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHB2	ENST00000535923.6	TSL:5 MANE Select	c.115T>C	p.Ser39Pro	missense	Exon 1 of 10	ENSP00000441875.1	Q99623-1
	PHB2	ENST00000925249.1		c.115T>C	p.Ser39Pro	missense	Exon 1 of 9	ENSP00000595308.1
	PHB2	ENST00000542912.5	TSL:5	c.115T>C	p.Ser39Pro	missense	Exon 1 of 8	ENSP00000440317.1	F5GY37

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.88	P
Vest4		0.82
MutPred		0.64		Gain of catalytic residue at V40 (P = 2e-04)
MVP		0.52
MPC		1.9
ClinPred		1.0	D
GERP RS		4.8
PromoterAI		-0.060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.83
gMVP		0.95
Mutation Taster		=39/61	disease causing

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: rs1555151894; hg19: chr12-7079592;