13-31148483-TAAAA-TAAAAAA

Position:

• chr13-31148483-TAAAA-TAAAAAA

Variant summary

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

The NM_006644.4(HSPH1):​c.1138-4_1138-3insTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 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: 0.00021 (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: -3.36

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 185 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPH1	NM_006644.4	c.1138-4_1138-3insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000320027.10	NP_006635.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPH1	ENST00000320027.10	c.1138-4_1138-3insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006644.4	ENSP00000318687	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 118998 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: 0.0000551 AC: 6 AN: 108980 Hom.: 0 AF XY: 0.0000166 AC XY: 1 AN XY: 60134

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000725

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000189

Gnomad NFE exome AF: 0.0000168

Gnomad OTH exome AF: 0.000509

GnomAD4 exome AF: 0.000214 AC: 185 AN: 865978 Hom.: 0 Cov.: 0 AF XY: 0.000200 AC XY: 87 AN XY: 434830

Gnomad4 AFR exome AF: 0.000322

Gnomad4 AMR exome AF: 0.000108

Gnomad4 ASJ exome AF: 0.000465

Gnomad4 EAS exome AF: 0.0000675

Gnomad4 SAS exome AF: 0.000333

Gnomad4 FIN exome AF: 0.000166

Gnomad4 NFE exome AF: 0.000216

Gnomad4 OTH exome AF: 0.000107

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 118998 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 56196

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

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;