13-31148483-TAAAAAAA-TAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006644.4(HSPH1):​c.1138-4delT 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (9623 hom., cov: 0)
  • Exomes 𝑓: 0.42 (3817 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPH1 NM_006644.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-31148483-TA-T is Benign according to our data. Variant chr13-31148483-TA-T is described in ClinVar as Benign. ClinVar VariationId is 402951.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

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.1138-4delT		splice_region intron	N/A	NP_006635.2
	HSPH1	NM_001286504.1		c.1144-4delT		splice_region intron	N/A	NP_001273433.1
	HSPH1	NM_001349704.2		c.1138-4delT		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.1138-4delT		splice_region intron	N/A	ENSP00000318687.5
	HSPH1	ENST00000630972.2	TSL:1	c.1144-4delT		splice_region intron	N/A	ENSP00000487365.1
	HSPH1	ENST00000380405.7	TSL:1	c.1138-4delT		splice_region intron	N/A	ENSP00000369768.4

Frequencies

GnomAD3 genomes AF: 0.416 AC: 49446 AN: 118872 Hom.: 9629 Cov.: 0

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.402

GnomAD2 exomes AF: 0.463 AC: 50425 AN: 108980 AF XY: 0.461

Gnomad AFR exome AF: 0.464

Gnomad AMR exome AF: 0.459

Gnomad ASJ exome AF: 0.443

Gnomad EAS exome AF: 0.448

Gnomad FIN exome AF: 0.468

Gnomad NFE exome AF: 0.468

Gnomad OTH exome AF: 0.470

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.423 AC: 361769 AN: 855930 Hom.: 3817 Cov.: 0 AF XY: 0.423 AC XY: 181729 AN XY: 429722

African (AFR) AF: 0.399 AC: 7301 AN: 18288

American (AMR) AF: 0.427 AC: 7767 AN: 18200

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 6195 AN: 14724

East Asian (EAS) AF: 0.410 AC: 11421 AN: 27830

South Asian (SAS) AF: 0.376 AC: 14551 AN: 38662

European-Finnish (FIN) AF: 0.433 AC: 15419 AN: 35584

Middle Eastern (MID) AF: 0.438 AC: 1773 AN: 4046

European-Non Finnish (NFE) AF: 0.426 AC: 281856 AN: 661748

Other (OTH) AF: 0.420 AC: 15486 AN: 36848

GnomAD4 genome AF: 0.416 AC: 49428 AN: 118860 Hom.: 9623 Cov.: 0 AF XY: 0.411 AC XY: 23075 AN XY: 56156

African (AFR) AF: 0.314 AC: 9673 AN: 30832

American (AMR) AF: 0.387 AC: 4215 AN: 10884

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1173 AN: 3044

East Asian (EAS) AF: 0.0241 AC: 80 AN: 3322

South Asian (SAS) AF: 0.233 AC: 777 AN: 3332

European-Finnish (FIN) AF: 0.467 AC: 2485 AN: 5318

Middle Eastern (MID) AF: 0.495 AC: 109 AN: 220

European-Non Finnish (NFE) AF: 0.499 AC: 29726 AN: 59514

Other (OTH) AF: 0.401 AC: 634 AN: 1580

Alfa AF: 0.193 Hom.: 372

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35594388; hg19: chr13-31722620;