9-125241509-GCC-GC

Variant names:

• chr9-125241509-GC-G
• rs3216733
• NM_005347.5:c.-384delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005347.5(HSPA5):​c.-384delG variant causes a upstream gene 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: 𝑓 0.71 (39647 hom., cov: 0)
• Consequence: HSPA5 NM_005347.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 11 publications found

Genes affected

HSPA5 (HGNC:5238): (heat shock protein family A (Hsp70) member 5) The protein encoded by this gene is a member of the heat shock protein 70 (HSP70) family. This protein localizes to the lumen of the endoplasmic reticulum (ER) where it operates as a typical HSP70 chaperone involved in the folding and assembly of proteins in the ER and is a master regulator of ER homeostasis. During cellular stress, as during viral infection or tumorogenesis, this protein interacts with the transmembrane stress sensor proteins PERK (protein kinase R-like endoplasmic reticulum kinase), IRE1 (inositol-requiring kinase 1), and ATF6 (activating transcription factor 6) where it acts as a repressor of the unfolded protein response (UPR) and also plays a role in cellular apoptosis and senescence. Elevated expression and atypical translocation of this protein to the cell surface has been reported in viral infections and some types of cancer cells. At the cell surface this protein may facilitate viral attachment and entry to host cells. This gene is a therapeutic target for the treatment of coronavirus diseases and chemoresistant cancers. [provided by RefSeq, Jul 2020]

HSPA5-DT (HGNC:55645): (HSPA5 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005347.5. 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
	HSPA5	NM_005347.5	MANE Select	c.-384delG		upstream_gene	N/A	NP_005338.1
	HSPA5-DT	NR_186826.1		n.-146delC		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA5	ENST00000324460.7	TSL:1 MANE Select	c.-384delG		upstream_gene	N/A	ENSP00000324173.6
	HSPA5	ENST00000680032.1		c.-384delG		upstream_gene	N/A	ENSP00000506285.1
	HSPA5	ENST00000680272.1		c.-384delG		upstream_gene	N/A	ENSP00000506097.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108169 AN: 151848 Hom.: 39592 Cov.: 0

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.694

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.713 AC: 108287 AN: 151966 Hom.: 39647 Cov.: 0 AF XY: 0.718 AC XY: 53314 AN XY: 74262

African (AFR) AF: 0.886 AC: 36769 AN: 41500

American (AMR) AF: 0.723 AC: 11029 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1997 AN: 3470

East Asian (EAS) AF: 0.703 AC: 3620 AN: 5152

South Asian (SAS) AF: 0.663 AC: 3198 AN: 4820

European-Finnish (FIN) AF: 0.756 AC: 7982 AN: 10556

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.611 AC: 41485 AN: 67906

Other (OTH) AF: 0.691 AC: 1452 AN: 2102

Alfa AF: 0.536 Hom.: 1397

Bravo AF: 0.722

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs3216733; hg19: chr9-128003788;