Variant chr19-35755641-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144617.3(HSPB6):c.364C>T(p.Arg122Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,534,108 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

HSPB6
NM_144617.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

Variant links:

Genes affected

HSPB6 (HGNC:26511): (heat shock protein family B (small) member 6) This locus encodes a heat shock protein. The encoded protein likely plays a role in smooth muscle relaxation. [provided by RefSeq, Jan 2012]

HSPB6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPB6	NM_144617.3 linkuse as main transcript	c.364C>T	p.Arg122Cys	missense_variant	3/3	ENST00000004982.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HSPB6	ENST00000004982.6 linkuse as main transcript	c.364C>T	p.Arg122Cys	missense_variant	3/3	1	NM_144617.3	P1
HSPB6	ENST00000592984.6 linkuse as main transcript	c.364C>T	p.Arg122Cys	missense_variant	4/4	4
HSPB6	ENST00000587965.1 linkuse as main transcript	c.*38C>T		3_prime_UTR_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000156

AC:

AN:

127994

Hom.:

AF XY:

0.0000143

AC XY:

AN XY:

69874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000424

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000318

AC:

AN:

1381928

Hom.:

Cov.:

AF XY:

0.0000396

AC XY:

AN XY:

681928

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:

0.0000409

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

Bravo

AF:

0.00000756

ExAC

AF:

0.0000285

AC:

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

Jan 04, 2022

The c.364C>T (p.R122C) alteration is located in exon 3 (coding exon 3) of the HSPB6 gene. This alteration results from a C to T substitution at nucleotide position 364, causing the arginine (R) at amino acid position 122 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

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

D;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.72

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.47

T;D

MetaSVM

Uncertain

0.65

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.7

D;.

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.017

D;D

Polyphen

1.0

D;.

Vest4

0.46

MutPred

0.49

Loss of MoRF binding (P = 0.0137);Loss of MoRF binding (P = 0.0137);

MVP

0.99

MPC

1.3

ClinPred

0.97

GERP RS

4.5

Varity_R

0.63

gMVP

0.71

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