rs35594388

Positions:

• chr13-31148483-TAAAA-T
• chr13-31148483-TAAAA-TA
• chr13-31148483-TAAAA-TAA
• chr13-31148483-TAAAA-TAAA
• chr13-31148483-TAAAA-TAAAAA
• chr13-31148483-TAAAA-TAAAAAA
• chr13-31148483-TAAAA-TAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006644.4(HSPH1):​c.1138-7_1138-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000791 in 864,602 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00079 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPH1 NM_006644.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 684 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPH1	NM_006644.4	c.1138-7_1138-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000320027.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPH1	ENST00000320027.10	c.1138-7_1138-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006644.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 118996 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000275 AC: 30 AN: 108980 Hom.: 0 AF XY: 0.000266 AC XY: 16 AN XY: 60134

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000419

Gnomad ASJ exome AF: 0.000363

Gnomad EAS exome AF: 0.000140

Gnomad SAS exome AF: 0.000518

Gnomad FIN exome AF: 0.000378

Gnomad NFE exome AF: 0.000219

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.000791 AC: 684 AN: 864602 Hom.: 0 AF XY: 0.000790 AC XY: 343 AN XY: 434118

Gnomad4 AFR exome AF: 0.000429

Gnomad4 AMR exome AF: 0.000595

Gnomad4 ASJ exome AF: 0.000733

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000923

Gnomad4 FIN exome AF: 0.000526

Gnomad4 NFE exome AF: 0.000850

Gnomad4 OTH exome AF: 0.000750

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 118996 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 56194

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs35594388; hg19: chr13-31722620;