chr12-6970430-T-G

Variant names:

• chr12-6970430-T-G
• rs1354438643
• NM_001144831.2:c.114A>C

Variant summary

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

The NM_001144831.2(PHB2):​c.114A>C​(p.Glu38Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHB2 NM_001144831.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24250272).

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.114A>C	p.Glu38Asp	missense	Exon 1 of 10	NP_001138303.1	Q99623-1
	PHB2	NM_001267700.1		c.114A>C	p.Glu38Asp	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.114A>C	p.Glu38Asp	missense	Exon 1 of 10	ENSP00000441875.1	Q99623-1
	PHB2	ENST00000925249.1		c.114A>C	p.Glu38Asp	missense	Exon 1 of 9	ENSP00000595308.1
	PHB2	ENST00000542912.5	TSL:5	c.114A>C	p.Glu38Asp	missense	Exon 1 of 8	ENSP00000440317.1	F5GY37

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.18
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.20
Sift	Benign	0.069	T
Sift4G	Benign	0.11	T
Polyphen		0.44	B
Vest4		0.57
MutPred		0.31		Gain of catalytic residue at E38 (P = 0)
MVP		0.37
MPC		0.86
ClinPred		0.44	T
GERP RS		-0.74
PromoterAI		-0.0082	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.20
gMVP		0.78
Mutation Taster		=69/31	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: rs1354438643; hg19: chr12-7079593;