12-6966468-T-A

Variant names:

• chr12-6966468-T-A
• rs34735201
• NM_001144831.2:c.822A>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001144831.2(PHB2):​c.822A>T​(p.Thr274Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T274T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHB2 NM_001144831.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12636384).
• BP7: Synonymous conserved (PhyloP=-0.779 with no splicing effect.

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.822A>T	p.Thr274Thr	synonymous	Exon 8 of 10	NP_001138303.1	Q99623-1
	PHB2	NM_001267700.1		c.708A>T	p.Thr236Thr	synonymous	Exon 7 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.822A>T	p.Thr274Thr	synonymous	Exon 8 of 10	ENSP00000441875.1	Q99623-1
	PHB2	ENST00000546111.5	TSL:2	c.245A>T	p.Gln82Leu	missense	Exon 3 of 4	ENSP00000438634.1	F5H2D2
	PHB2	ENST00000925249.1		c.822A>T	p.Thr274Thr	synonymous	Exon 8 of 9	ENSP00000595308.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.50
DANN	Benign	0.69
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.78
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.062
Sift	Benign	0.043	D
Vest4		0.23
MutPred		0.56		Gain of catalytic residue at S81 (P = 0)
MVP		0.20
ClinPred		0.15	T
GERP RS		-12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs34735201; hg19: chr12-7075631;