7-76302721-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001540.5(HSPB1):āc.9G>Cā(p.Glu3Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,450,104 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E3E) has been classified as Benign.
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
HSPB1
NM_001540.5 missense
NM_001540.5 missense
Scores
3
10
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.60
Genes affected
HSPB1 (HGNC:5246): (heat shock protein family B (small) member 1) This gene encodes a member of the small heat shock protein (HSP20) family of proteins. In response to environmental stress, the encoded protein translocates from the cytoplasm to the nucleus and functions as a molecular chaperone that promotes the correct folding of other proteins. This protein plays an important role in the differentiation of a wide variety of cell types. Expression of this gene is correlated with poor clinical outcome in multiple human cancers, and the encoded protein may promote cancer cell proliferation and metastasis, while protecting cancer cells from apoptosis. Mutations in this gene have been identified in human patients with Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a chain Heat shock protein beta-1 (size 204) in uniprot entity HSPB1_HUMAN there are 34 pathogenic changes around while only 2 benign (94%) in NM_001540.5
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000424 AC: 1AN: 235782Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130326
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GnomAD4 exome AF: 0.00000138 AC: 2AN: 1450104Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 721836
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.1148);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at