rs12009

Variant names:

• chr9-125235024-G-A
• rs12009
• NM_005347.5:c.*1568C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-125235024-G-A
• chr9-125235024-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005347.5(HSPA5):​c.*1568C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,706 control chromosomes in the GnomAD database, including 22,443 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (22441 hom., cov: 29)
  • Exomes 𝑓: 0.38 (2 hom.)
• Consequence: HSPA5 NM_005347.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 31 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.624 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA5	NM_005347.5	MANE Select	c.*1568C>T		3_prime_UTR	Exon 8 of 8	NP_005338.1	P11021

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA5	ENST00000324460.7	TSL:1 MANE Select	c.*1568C>T		3_prime_UTR	Exon 8 of 8	ENSP00000324173.6	P11021
	HSPA5	ENST00000680272.1		c.*1568C>T		3_prime_UTR	Exon 8 of 8	ENSP00000506097.1	A0A7P0TAI0
	HSPA5	ENST00000930639.1		c.*1568C>T		3_prime_UTR	Exon 7 of 7	ENSP00000600698.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81832 AN: 151572 Hom.: 22426 Cov.: 29

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.375 AC: 6 AN: 16 Hom.: 2 Cov.: 0 AF XY: 0.333 AC XY: 4 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.429 AC: 6 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.540 AC: 81882 AN: 151690 Hom.: 22441 Cov.: 29 AF XY: 0.546 AC XY: 40471 AN XY: 74130

African (AFR) AF: 0.481 AC: 19903 AN: 41350

American (AMR) AF: 0.635 AC: 9636 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1621 AN: 3466

East Asian (EAS) AF: 0.548 AC: 2819 AN: 5144

South Asian (SAS) AF: 0.543 AC: 2619 AN: 4824

European-Finnish (FIN) AF: 0.659 AC: 6936 AN: 10528

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36537 AN: 67888

Other (OTH) AF: 0.551 AC: 1160 AN: 2104

Alfa AF: 0.530 Hom.: 30132

Bravo AF: 0.536

Asia WGS AF: 0.541 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.63
PhyloP100		1.1
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: rs12009; hg19: chr9-127997303;