14-102084823-ATCT-A

Position:

• chr14-102084823-ATCT-A

Variant summary

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

The NM_005348.4(HSP90AA1):​c.836_838delAGA​(p.Lys279del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000805 in 151,620 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00080 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSP90AA1 NM_005348.4 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.81

Genes affected

HSP90AA1 (HGNC:5253): (heat shock protein 90 alpha family class A member 1) The protein encoded by this gene is an inducible molecular chaperone that functions as a homodimer. The encoded protein aids in the proper folding of specific target proteins by use of an ATPase activity that is modulated by co-chaperones. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

HSP90AA1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 122 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSP90AA1	NM_005348.4	c.836_838delAGA	p.Lys279del	disruptive_inframe_deletion	5/11	ENST00000216281.13	NP_005339.3
HSP90AA1	NM_001017963.3	c.1202_1204delAGA	p.Lys401del	disruptive_inframe_deletion	6/12		NP_001017963.2
HSP90AA1	XM_011536718.3	c.1199_1201delAGA	p.Lys400del	disruptive_inframe_deletion	6/12		XP_011535020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSP90AA1	ENST00000216281.13	c.836_838delAGA	p.Lys279del	disruptive_inframe_deletion	5/11	1	NM_005348.4	ENSP00000216281.8

Frequencies

GnomAD3 genomes AF: 0.000805 AC: 122 AN: 151502 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.000833

Gnomad FIN AF: 0.000287

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000354

Gnomad OTH AF: 0.00144

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00177 AC: 2536 AN: 1432986 Hom.: 0 AF XY: 0.00166 AC XY: 1184 AN XY: 713348

Gnomad4 AFR exome AF: 0.00213

Gnomad4 AMR exome AF: 0.00286

Gnomad4 ASJ exome AF: 0.000743

Gnomad4 EAS exome AF: 0.000615

Gnomad4 SAS exome AF: 0.000821

Gnomad4 FIN exome AF: 0.000190

Gnomad4 NFE exome AF: 0.00194

Gnomad4 OTH exome AF: 0.00145

GnomAD4 genome AF: 0.000805 AC: 122 AN: 151620 Hom.: 1 Cov.: 32 AF XY: 0.000729 AC XY: 54 AN XY: 74080

Gnomad4 AFR AF: 0.00143

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000968

Gnomad4 SAS AF: 0.000833

Gnomad4 FIN AF: 0.000287

Gnomad4 NFE AF: 0.000354

Gnomad4 OTH AF: 0.00143

Bravo AF: 0.000960

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hepatocellular carcinoma Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs747755226; hg19: chr14-102551160;