chr13-31143849-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006644.4(HSPH1):ā€‹c.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

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49
Variant links:
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]

Genome browser will be placed here

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
HSPH1NM_006644.4 linkuse as main transcriptc.1659G>C p.Gln553His missense_variant 12/18 ENST00000320027.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HSPH1ENST00000320027.10 linkuse as main transcriptc.1659G>C p.Gln553His missense_variant 12/181 NM_006644.4 P1Q92598-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
249996
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135142
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000530
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1459520
Hom.:
0
Cov.:
30
AF XY:
0.00000964
AC XY:
7
AN XY:
726062
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000151
ExAC
AF:
0.0000412
AC:
5

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 GeneticsFeb 22, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.51
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.028
T;T;.
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
.;L;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.2
.;N;.
REVEL
Benign
0.14
Sift
Benign
0.051
.;T;.
Sift4G
Benign
0.093
T;T;T
Polyphen
0.0020
.;B;.
Vest4
0.28
MutPred
0.23
.;Gain of glycosylation at T551 (P = 0.0591);.;
MVP
0.41
MPC
0.39
ClinPred
0.16
T
GERP RS
5.8
Varity_R
0.14
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs765149973; hg19: chr13-31717986; API