GeneBe

rs35594388

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006644.4(HSPH1):​c.1138-10_1138-4delTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 866,362 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

HSPH1
NM_006644.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.797

Publications

0 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSPH1NM_006644.4 linkc.1138-10_1138-4delTTTTTTT splice_region_variant, intron_variant Intron 8 of 17 ENST00000320027.10 NP_006635.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSPH1ENST00000320027.10 linkc.1138-10_1138-4delTTTTTTT splice_region_variant, intron_variant Intron 8 of 17 1 NM_006644.4 ENSP00000318687.5
HSPH1ENST00000602786.5 linkn.*666-10_*666-4delTTTTTTT splice_region_variant, intron_variant Intron 7 of 16 1 ENSP00000473512.1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.00000346
AC:
3
AN:
866362
Hom.:
0
AF XY:
0.00000460
AC XY:
2
AN XY:
435038
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
18658
American (AMR)
AF:
0.00
AC:
0
AN:
18506
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15046
East Asian (EAS)
AF:
0.00
AC:
0
AN:
29652
South Asian (SAS)
AF:
0.0000512
AC:
2
AN:
39066
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
36188
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4108
European-Non Finnish (NFE)
AF:
0.00000150
AC:
1
AN:
667730
Other (OTH)
AF:
0.00
AC:
0
AN:
37408
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs35594388; hg19: chr13-31722620; API