chr17-49409410-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000300408.8(PHB1):​c.314G>A​(p.Arg105His) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PHB1
ENST00000300408.8 missense

Scores

3
5
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.12
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33489168).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PHB1NM_002634.4 linkuse as main transcriptc.314G>A p.Arg105His missense_variant 4/7 ENST00000300408.8 NP_002625.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PHB1ENST00000300408.8 linkuse as main transcriptc.314G>A p.Arg105His missense_variant 4/71 NM_002634.4 ENSP00000300408 P1P35232-1
ENST00000576461.1 linkuse as main transcriptn.270+36324C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152040
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251458
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461744
Hom.:
0
Cov.:
32
AF XY:
0.00000825
AC XY:
6
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152040
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74228
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Pathogenic
0.14
CADD
Uncertain
25
DANN
Benign
0.96
DEOGEN2
Uncertain
0.64
D;D;.;D;.;D;D;.;.
Eigen
Benign
-0.20
Eigen_PC
Benign
0.012
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.75
T;.;T;.;T;T;T;T;T
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.33
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
0.082
D
MutationAssessor
Benign
0.14
N;N;N;N;.;.;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.4
.;.;N;N;N;N;N;N;N
REVEL
Uncertain
0.50
Sift
Benign
0.55
.;.;T;T;T;T;T;T;T
Sift4G
Benign
0.43
T;T;T;T;T;.;T;.;.
Polyphen
0.0010
B;B;.;B;.;.;.;.;.
Vest4
0.74
MutPred
0.33
Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP
0.95
MPC
1.1
ClinPred
0.43
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121918372; hg19: chr17-47486772; COSMIC: COSV55931780; COSMIC: COSV55931780; API