13-31148483-TAAAAAAA-TAAAA

Variant names:

• chr13-31148483-TAAA-T
• rs35594388
• NM_006644.4:c.1138-6_1138-4delTTT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_006644.4(HSPH1):​c.1138-6_1138-4delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00918 in 973,754 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000050 (0 hom., cov: 0)
  • Exomes 𝑓: 0.010 (0 hom.)
• Consequence: HSPH1 NM_006644.4 splice_region, 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 -5 ACMG points.

• BP6: Variant 13-31148483-TAAA-T is Benign according to our data. Variant chr13-31148483-TAAA-T is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPH1	NM_006644.4	c.1138-6_1138-4delTTT		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.1138-6_1138-4delTTT		splice_region_variant, intron_variant	Intron 8 of 17	1	NM_006644.4	ENSP00000318687.5
HSPH1	ENST00000602786.5	n.*666-6_*666-4delTTT		splice_region_variant, intron_variant	Intron 7 of 16	1		ENSP00000473512.1

Frequencies

GnomAD3 genomes AF: 0.0000504 AC: 6 AN: 118980 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000918

Gnomad ASJ AF: 0.000328

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000336

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00457 AC: 498 AN: 108980 Hom.: 0 AF XY: 0.00496 AC XY: 298 AN XY: 60134

Gnomad AFR exome AF: 0.00164

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.0120

Gnomad EAS exome AF: 0.00154

Gnomad SAS exome AF: 0.00632

Gnomad FIN exome AF: 0.00435

Gnomad NFE exome AF: 0.00503

Gnomad OTH exome AF: 0.00305

GnomAD4 exome AF: 0.0104 AC: 8930 AN: 854774 Hom.: 0 AF XY: 0.0106 AC XY: 4540 AN XY: 429212

Gnomad4 AFR exome AF: 0.00585

Gnomad4 AMR exome AF: 0.00565

Gnomad4 ASJ exome AF: 0.00928

Gnomad4 EAS exome AF: 0.00180

Gnomad4 SAS exome AF: 0.00875

Gnomad4 FIN exome AF: 0.00865

Gnomad4 NFE exome AF: 0.0113

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0000504 AC: 6 AN: 118980 Hom.: 0 Cov.: 0 AF XY: 0.0000534 AC XY: 3 AN XY: 56184

Gnomad4 AFR AF: 0.0000324

Gnomad4 AMR AF: 0.0000918

Gnomad4 ASJ AF: 0.000328

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.0000336

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)		0.030		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;