17-49405020-T-C

Variant names:

• chr17-49405020-T-C
• rs2143256481
• NM_002634.4:c.791A>G

Variant summary

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

The NM_002634.4(PHB1):​c.791A>G​(p.Gln264Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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: PHB1 NM_002634.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.99
• Publications: 0 publications found

Genes affected

PHB1 (HGNC:8912): (prohibitin 1) This gene is evolutionarily conserved, and its product is proposed to play a role in human cellular senescence and tumor suppression. Antiproliferative activity is reported to be localized to the 3' UTR, which is proposed to function as a trans-acting regulatory RNA. Several pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ENSG00000250186 (HGNC:):

ZNF652-AS1 (HGNC:55582): (ZNF652 antisense RNA 1)

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_002634.4. 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
	PHB1	NM_002634.4	MANE Select	c.791A>G	p.Gln264Arg	missense	Exon 7 of 7	NP_002625.1	P35232-1
	PHB1	NM_001281496.2		c.791A>G	p.Gln264Arg	missense	Exon 7 of 7	NP_001268425.1	P35232-1
	PHB1	NM_001281715.2		c.791A>G	p.Gln264Arg	missense	Exon 8 of 8	NP_001268644.1	P35232-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHB1	ENST00000300408.8	TSL:1 MANE Select	c.791A>G	p.Gln264Arg	missense	Exon 7 of 7	ENSP00000300408.3	P35232-1
	PHB1	ENST00000511832.6	TSL:2	c.791A>G	p.Gln264Arg	missense	Exon 7 of 7	ENSP00000425035.2	P35232-1
	PHB1	ENST00000419140.7	TSL:5	c.791A>G	p.Gln264Arg	missense	Exon 7 of 7	ENSP00000393320.3	P35232-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	0.036
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0076	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		8.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.27	N
REVEL	Uncertain	0.29
Sift	Benign	0.29	T
Sift4G	Benign	0.30	T
Polyphen		0.010	B
Vest4		0.73
MutPred		0.34		Gain of catalytic residue at S265 (P = 0.0545)
MVP		0.82
MPC		0.95
ClinPred		0.76	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.99

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: rs2143256481; hg19: chr17-47482382;