rs377573215

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004064.5(CDKN1B):​c.387T>A​(p.His129Gln) 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. 12/21 in silico tools predict a benign outcome for this variant. 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. H129R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CDKN1B
NM_004064.5 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253
Variant links:
Genes affected
CDKN1B (HGNC:1785): (cyclin dependent kinase inhibitor 1B) This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. The degradation of this protein, which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes, is required for the cellular transition from quiescence to the proliferative state. Mutations in this gene are associated with multiple endocrine neoplasia type IV (MEN4). [provided by RefSeq, Apr 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21891546).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDKN1BNM_004064.5 linkuse as main transcriptc.387T>A p.His129Gln missense_variant 1/3 ENST00000228872.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDKN1BENST00000228872.9 linkuse as main transcriptc.387T>A p.His129Gln missense_variant 1/31 NM_004064.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
39
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Uncertain
0.015
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
13
DANN
Benign
0.96
DEOGEN2
Benign
0.33
T;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.75
T;T
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-0.29
T
MutationAssessor
Uncertain
2.1
M;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.0
N;N
REVEL
Uncertain
0.36
Sift
Benign
0.097
T;T
Sift4G
Benign
0.51
T;T
Polyphen
1.0
D;.
Vest4
0.38
MutPred
0.16
Gain of relative solvent accessibility (P = 0.1066);Gain of relative solvent accessibility (P = 0.1066);
MVP
0.76
MPC
0.29
ClinPred
0.68
D
GERP RS
-7.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.080
gMVP
0.33

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-12871160; API