Variant 14-102083261-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005348.4(HSP90AA1):c.1528C>T(p.Arg510Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

HSP90AA1
NM_005348.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.36

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSP90AA1	NM_005348.4 linkuse as main transcript	c.1528C>T	p.Arg510Cys	missense_variant	9/11	ENST00000216281.13	NP_005339.3	P07900-1K9JA46
HSP90AA1	NM_001017963.3 linkuse as main transcript	c.1894C>T	p.Arg632Cys	missense_variant	10/12		NP_001017963.2	P07900-2Q86SX1
HSP90AA1	XM_011536718.3 linkuse as main transcript	c.1891C>T	p.Arg631Cys	missense_variant	10/12		XP_011535020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HSP90AA1	ENST00000216281.13 linkuse as main transcript	c.1528C>T	p.Arg510Cys	missense_variant	9/11	1	NM_005348.4	ENSP00000216281.8	P07900-1
HSP90AA1	ENST00000334701.11 linkuse as main transcript	c.1894C>T	p.Arg632Cys	missense_variant	10/12	1		ENSP00000335153.7	P07900-2
HSP90AA1	ENST00000554401.1 linkuse as main transcript	n.*957C>T		non_coding_transcript_exon_variant	7/7	1		ENSP00000451400.1	H0YJF5
HSP90AA1	ENST00000554401.1 linkuse as main transcript	n.*957C>T		3_prime_UTR_variant	7/7	1		ENSP00000451400.1	H0YJF5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251348

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.1528C>T (p.R510C) alteration is located in exon 9 (coding exon 8) of the HSP90AA1 gene. This alteration results from a C to T substitution at nucleotide position 1528, causing the arginine (R) at amino acid position 510 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.69

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

M;.

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.045

D;D

Polyphen

0.40

B;P

Vest4

0.90

MutPred

0.45

Gain of catalytic residue at L511 (P = 0.0026);.;

MVP

0.89

ClinPred

0.93

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.76

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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