Genetic Variant HSPB6:p.Ala158Thr (chr19-35755533-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144617.3(HSPB6):c.472G>A(p.Ala158Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000767 in 1,499,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

HSPB6
NM_144617.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

Publications

0 publications found

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:

ENSG00000267328 (HGNC:):

ENSG00000267328 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13894677).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144617.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB6	NM_144617.3	MANE Select	c.472G>A	p.Ala158Thr	missense	Exon 3 of 3	NP_653218.1	O14558

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSPB6	ENST00000004982.6	TSL:1 MANE Select	c.472G>A	p.Ala158Thr	missense	Exon 3 of 3	ENSP00000004982.3	O14558
HSPB6	ENST00000906439.1		c.349G>A	p.Ala117Thr	missense	Exon 2 of 2	ENSP00000576498.1
HSPB6	ENST00000587965.1	TSL:2	c.*146G>A		3_prime_UTR	Exon 2 of 2	ENSP00000467169.1	K7EP04

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151692

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000625

AC:

AN:

112042

AF XY:

0.0000323

show subpopulations

Gnomad AFR exome

AF:

0.000215

Gnomad AMR exome

AF:

0.0000490

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000816

AC:

110

AN:

1347762

Hom.:

Cov.:

AF XY:

0.0000723

AC XY:

AN XY:

664232

show subpopulations

African (AFR)

AF:

0.0000684

AC:

AN:

29238

American (AMR)

AF:

0.00

AC:

AN:

31702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23538

East Asian (EAS)

AF:

0.00

AC:

AN:

33310

South Asian (SAS)

AF:

0.00

AC:

AN:

76440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5482

European-Non Finnish (NFE)

AF:

0.0000989

AC:

105

AN:

1061372

Other (OTH)

AF:

0.0000538

AC:

AN:

55772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151692

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74064

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41336

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5068

South Asian (SAS)

AF:

0.00

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67878

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000869

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.065

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.53

M_CAP

Benign

0.051

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.49

MutationAssessor

Benign

0.0

PhyloP100

2.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.46

REVEL

Benign

0.22

Sift

Benign

0.41

Sift4G

Uncertain

0.025

Polyphen

0.13

Vest4

0.22

MutPred

0.31

Gain of glycosylation at A158 (P = 0.0017)

MVP

0.95

ClinPred

0.027

GERP RS

3.5

Varity_R

0.055

gMVP

0.36

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over