12-6967700-CTC-TTG

Variant names:

• chr12-6967700-CTC-TTG
• NM_001144831.2:c.685_687delGAGinsCAA
• PHB2 p.Glu229Gln

Variant summary

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

The NM_001144831.2(PHB2):​c.685_687delGAGinsCAA​(p.Glu229Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. E229K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHB2 NM_001144831.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10
• 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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.685_687delGAGinsCAA	p.Glu229Gln	missense	N/A	NP_001138303.1	Q99623-1
	PHB2	NM_001267700.1		c.607+190_607+192delGAGinsCAA		intron	N/A	NP_001254629.1	Q99623-2
	SCARNA12	NR_003010.1		n.-96_-94delGAGinsCAA		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHB2	ENST00000535923.6	TSL:5 MANE Select	c.685_687delGAGinsCAA	p.Glu229Gln	missense	N/A	ENSP00000441875.1	Q99623-1
	PHB2	ENST00000925249.1		c.685_687delGAGinsCAA	p.Glu229Gln	missense	N/A	ENSP00000595308.1
	PHB2	ENST00000542912.5	TSL:5	c.685_687delGAGinsCAA	p.Glu229Gln	missense	N/A	ENSP00000440317.1	F5GY37

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-7076863;