13-31148483-TAAAAAAA-TAAAAAAAAAA

Variant names:

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

Variant summary

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

The NM_006644.4(HSPH1):​c.1138-6_1138-4dupTTT variant causes a splice region, 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: not found (cov: 0)
  • Exomes 𝑓: 0.000023 (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 GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPH1	NM_006644.4	c.1138-6_1138-4dupTTT		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_1138-3insTTT		splice_region_variant, intron_variant	Intron 8 of 17	1	NM_006644.4	ENSP00000318687.5
HSPH1	ENST00000602786.5	n.*666-4_*666-3insTTT		splice_region_variant, intron_variant	Intron 7 of 16	1		ENSP00000473512.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000231 AC: 20 AN: 866344 Hom.: 0 Cov.: 0 AF XY: 0.0000184 AC XY: 8 AN XY: 435024

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000540

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000337

Gnomad4 SAS exome AF: 0.0000512

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.0000267

GnomAD4 genome Cov.: 0

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-31722620;