Variant 14-102085795-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005348.4(HSP90AA1):c.492C>T(p.Ser164Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,613,914 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 8 hom. )

Consequence

HSP90AA1
NM_005348.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.09

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 14-102085795-G-A is Benign according to our data. Variant chr14-102085795-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644576.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BS2

High AC in GnomAd4 at 251 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSP90AA1	NM_005348.4 linkuse as main transcript	c.492C>T	p.Ser164Ser	synonymous_variant	3/11	ENST00000216281.13	NP_005339.3	P07900-1K9JA46
HSP90AA1	NM_001017963.3 linkuse as main transcript	c.858C>T	p.Ser286Ser	synonymous_variant	4/12		NP_001017963.2	P07900-2Q86SX1
HSP90AA1	XM_011536718.3 linkuse as main transcript	c.855C>T	p.Ser285Ser	synonymous_variant	4/12		XP_011535020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HSP90AA1	ENST00000216281.13 linkuse as main transcript	c.492C>T	p.Ser164Ser	synonymous_variant	3/11	1	NM_005348.4	ENSP00000216281.8	P07900-1
HSP90AA1	ENST00000334701.11 linkuse as main transcript	c.858C>T	p.Ser286Ser	synonymous_variant	4/12	1		ENSP00000335153.7	P07900-2
HSP90AA1	ENST00000554401.1 linkuse as main transcript	n.115-364C>T		intron_variant		1		ENSP00000451400.1	H0YJF5
HSP90AA1	ENST00000553585.5 linkuse as main transcript	c.322+170C>T		intron_variant		3		ENSP00000450712.1	G3V2J8

Frequencies

GnomAD3 genomes

AF:

0.00165

AC:

251

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00185

AC:

464

AN:

251098

Hom.:

AF XY:

0.00169

AC XY:

230

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.00189

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00195

AC:

2845

AN:

1461654

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

1374

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00977

Gnomad4 NFE exome

AF:

0.00201

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00165

AC:

251

AN:

152260

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0126

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00142

Hom.:

Bravo

AF:

0.000767

EpiCase

AF:

0.00136

EpiControl

AF:

0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

HSP90AA1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.5

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over