chr13-31148483-T-TAAAA

Variant names:

• chr13-31148483-T-TAAAA
• rs35594388
• NM_006644.4:c.1138-7_1138-4dupTTTT

Variant summary

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

The NM_006644.4(HSPH1):​c.1138-7_1138-4dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: HSPH1 NM_006644.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.36
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006644.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPH1	NM_006644.4	MANE Select	c.1138-7_1138-4dupTTTT		splice_region intron	N/A	NP_006635.2
	HSPH1	NM_001286504.1		c.1144-7_1144-4dupTTTT		splice_region intron	N/A	NP_001273433.1
	HSPH1	NM_001349704.2		c.1138-7_1138-4dupTTTT		splice_region intron	N/A	NP_001336633.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPH1	ENST00000320027.10	TSL:1 MANE Select	c.1138-4_1138-3insTTTT		splice_region intron	N/A	ENSP00000318687.5
	HSPH1	ENST00000630972.2	TSL:1	c.1144-4_1144-3insTTTT		splice_region intron	N/A	ENSP00000487365.1
	HSPH1	ENST00000380405.7	TSL:1	c.1138-4_1138-3insTTTT		splice_region intron	N/A	ENSP00000369768.4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000104 AC: 9 AN: 866378 Hom.: 0 Cov.: 0 AF XY: 0.00000919 AC XY: 4 AN XY: 435040

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000536 AC: 1 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: 0.0000256 AC: 1 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: 0.0000105 AC: 7 AN: 667746

Other (OTH) AF: 0.00 AC: 0 AN: 37408

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000160964), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.4

Splicing

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

Other links and lift over

dbSNP: rs35594388; hg19: chr13-31722620;