6-31829604-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005346.6(HSPA1B):c.1654G>A(p.Ala552Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.000010 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HSPA1B
NM_005346.6 missense
NM_005346.6 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 5.20
Genes affected
HSPA1B (HGNC:5233): (heat shock protein family A (Hsp70) member 1B) This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins. [provided by RefSeq, Jul 2008]
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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=0.08087477).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSPA1B | NM_005346.6 | c.1654G>A | p.Ala552Thr | missense_variant | 1/1 | ENST00000375650.5 | NP_005337.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HSPA1B | ENST00000375650.5 | c.1654G>A | p.Ala552Thr | missense_variant | 1/1 | 6 | NM_005346.6 | ENSP00000364801.3 | ||
ENSG00000285565 | ENST00000649802.1 | n.771G>A | non_coding_transcript_exon_variant | 1/4 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD3 exomes AF: 0.00000816 AC: 2AN: 245220Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133828
GnomAD3 exomes
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000103 AC: 15AN: 1460188Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7AN XY: 726406
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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30
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GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ExAC
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2022 | The c.1654G>A (p.A552T) alteration is located in exon 1 (coding exon 1) of the HSPA1B gene. This alteration results from a G to A substitution at nucleotide position 1654, causing the alanine (A) at amino acid position 552 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Gain of phosphorylation at A552 (P = 0.0699);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at