chr13-31143849-C-G
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006644.4(HSPH1):āc.1659G>Cā(p.Gln553His) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,459,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.000012 ( 0 hom. )
Consequence
HSPH1
NM_006644.4 missense
NM_006644.4 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 5.49
Genes affected
HSPH1 (HGNC:16969): (heat shock protein family H (Hsp110) member 1) This gene encodes a member of the heat shock protein 70 family of proteins. The encoded protein functions as a nucleotide exchange factor for the molecular chaperone heat shock cognate 71 kDa protein (Hsc70). In addition, this protein plays a distinct but related role as a holdase that inhibits the aggregation of misfolded proteins, including the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Elevated expression of this protein has been observed in numerous human cancers. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.21162769).
BS2
High AC in GnomAdExome4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPH1 | NM_006644.4 | c.1659G>C | p.Gln553His | missense_variant | 12/18 | ENST00000320027.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPH1 | ENST00000320027.10 | c.1659G>C | p.Gln553His | missense_variant | 12/18 | 1 | NM_006644.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249996Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135142
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1459520Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7AN XY: 726062
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GnomAD4 genome Cov.: 32
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32
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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 | Feb 22, 2023 | The c.1659G>C (p.Q553H) alteration is located in exon 12 (coding exon 12) of the HSPH1 gene. This alteration results from a G to C substitution at nucleotide position 1659, causing the glutamine (Q) at amino acid position 553 to be replaced by a histidine (H). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;.
REVEL
Benign
Sift
Benign
.;T;.
Sift4G
Benign
T;T;T
Polyphen
0.0020
.;B;.
Vest4
MutPred
0.23
.;Gain of glycosylation at T551 (P = 0.0591);.;
MVP
MPC
0.39
ClinPred
T
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