13-31148483-TAAAAAAA-TAAAAAAAA

Variant names:

• chr13-31148483-T-TA
• rs35594388
• NM_006644.4:c.1138-4dupT

Variant summary

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

The NM_006644.4(HSPH1):​c.1138-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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 0.0017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0098 (0 hom.)
• Consequence: HSPH1 NM_006644.4 splice_region, 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 GnomAd4 at 207 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPH1	NM_006644.4	c.1138-4dupT		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
HSPH1	ENST00000320027.10	c.1138-4_1138-3insT		splice_region_variant, intron_variant	Intron 8 of 17	1	NM_006644.4	ENSP00000318687.5
HSPH1	ENST00000602786.5	n.*666-4_*666-3insT		splice_region_variant, intron_variant	Intron 7 of 16	1		ENSP00000473512.1

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 207 AN: 118990 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00402

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000826

Gnomad ASJ AF: 0.000328

Gnomad EAS AF: 0.00390

Gnomad SAS AF: 0.00299

Gnomad FIN AF: 0.000940

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000738

Gnomad OTH AF: 0.000635

GnomAD3 exomes AF: 0.00289 AC: 315 AN: 108980 Hom.: 0 AF XY: 0.00279 AC XY: 168 AN XY: 60134

Gnomad AFR exome AF: 0.00367

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00363

Gnomad EAS exome AF: 0.00601

Gnomad SAS exome AF: 0.00487

Gnomad FIN exome AF: 0.00473

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.00356

GnomAD4 exome AF: 0.00977 AC: 8450 AN: 864572 Hom.: 0 Cov.: 0 AF XY: 0.00956 AC XY: 4152 AN XY: 434136

Gnomad4 AFR exome AF: 0.0137

Gnomad4 AMR exome AF: 0.00542

Gnomad4 ASJ exome AF: 0.00747

Gnomad4 EAS exome AF: 0.0110

Gnomad4 SAS exome AF: 0.0152

Gnomad4 FIN exome AF: 0.00693

Gnomad4 NFE exome AF: 0.00965

Gnomad4 OTH exome AF: 0.00940

GnomAD4 genome AF: 0.00174 AC: 207 AN: 118976 Hom.: 0 Cov.: 0 AF XY: 0.00165 AC XY: 93 AN XY: 56202

Gnomad4 AFR AF: 0.00402

Gnomad4 AMR AF: 0.000826

Gnomad4 ASJ AF: 0.000328

Gnomad4 EAS AF: 0.00391

Gnomad4 SAS AF: 0.00300

Gnomad4 FIN AF: 0.000940

Gnomad4 NFE AF: 0.000738

Gnomad4 OTH AF: 0.000631

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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;