6-31829604-G-A

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

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20
Variant links:
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]

Genome browser will be placed here

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
HSPA1BNM_005346.6 linkuse as main transcriptc.1654G>A p.Ala552Thr missense_variant 1/1 ENST00000375650.5 NP_005337.2 P0DMV8-1P0DMV9A8K5I0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HSPA1BENST00000375650.5 linkuse as main transcriptc.1654G>A p.Ala552Thr missense_variant 1/16 NM_005346.6 ENSP00000364801.3 P0DMV9
ENSG00000285565ENST00000649802.1 linkuse as main transcriptn.771G>A non_coding_transcript_exon_variant 1/4

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.00000816
AC:
2
AN:
245220
Hom.:
0
AF XY:
0.00000747
AC XY:
1
AN XY:
133828
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000582
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
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000103
AC:
15
AN:
1460188
Hom.:
0
Cov.:
30
AF XY:
0.00000964
AC XY:
7
AN XY:
726406
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.0000108
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
22
ExAC
AF:
0.00000852
AC:
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 submitterclinical testingAmbry GeneticsDec 21, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.0030
T
Eigen
Benign
0.078
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.78
D
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.081
T
MetaSVM
Benign
-0.96
T
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
0.77
N
REVEL
Benign
0.069
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Vest4
0.14
MutPred
0.32
Gain of phosphorylation at A552 (P = 0.0699);
MVP
0.12
ClinPred
0.50
T
GERP RS
4.1
Varity_R
0.12
gMVP
0.48

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

LitVar

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

Other links and lift over

dbSNP: rs759701257; hg19: chr6-31797381; API