Variant rs780878780 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2

The NM_001540.5(HSPB1):c.45C>A(p.Ser15Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000687 in 1,454,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

HSPB1
NM_001540.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.39

Variant links:

Genes affected

HSPB1 (HGNC:5246): (heat shock protein family B (small) member 1) This gene encodes a member of the small heat shock protein (HSP20) family of proteins. In response to environmental stress, the encoded protein translocates from the cytoplasm to the nucleus and functions as a molecular chaperone that promotes the correct folding of other proteins. This protein plays an important role in the differentiation of a wide variety of cell types. Expression of this gene is correlated with poor clinical outcome in multiple human cancers, and the encoded protein may promote cancer cell proliferation and metastasis, while protecting cancer cells from apoptosis. Mutations in this gene have been identified in human patients with Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. [provided by RefSeq, Aug 2017]

HSPB1 links:

HSPB1 (HGNC:):

HSPB1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a modified_residue Phosphoserine; by MAPKAPK2 and MAPKAPK3 (size 0) in uniprot entity HSPB1_HUMAN

PP3

MetaRNN computational evidence supports a deleterious effect, 0.876

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPB1	NM_001540.5 linkuse as main transcript	c.45C>A	p.Ser15Arg	missense_variant	1/3	ENST00000248553.7	NP_001531.1	P04792V9HW43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPB1	ENST00000248553.7 linkuse as main transcript	c.45C>A	p.Ser15Arg	missense_variant	1/3	1	NM_001540.5	ENSP00000248553.6		P04792

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000687

AC:

AN:

1454800

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

724020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000900

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease axonal type 2F

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

May 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.79

MetaRNN

Pathogenic

0.88

MetaSVM

Uncertain

0.64

MutationAssessor

Benign

1.5

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.5

REVEL

Pathogenic

0.74

Sift

Uncertain

0.0060

Sift4G

Benign

0.093

Polyphen

1.0

Vest4

0.79

MutPred

0.49

Gain of MoRF binding (P = 0.0251);

MVP

0.96

MPC

1.4

ClinPred

0.98

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.88

gMVP

0.92

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