rs1122326

Positions:

• chr17-42122855-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033194.3(HSPB9):​c.5A>C​(p.Gln2Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,604,988 control chromosomes in the GnomAD database, including 52,820 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.33 (10566 hom., cov: 33)
  • Exomes 𝑓: 0.23 (42254 hom.)
• Consequence: HSPB9 NM_033194.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.757

Genes affected

HSPB9 (HGNC:30589): (heat shock protein family B (small) member 9) Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.1186435E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPB9	NM_033194.3	c.5A>C	p.Gln2Pro	missense_variant	1/1	ENST00000565659.2	NP_149971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPB9	ENST00000565659.2	c.5A>C	p.Gln2Pro	missense_variant	1/1		NM_033194.3	ENSP00000458018	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50104 AN: 152112 Hom.: 10552 Cov.: 33

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.296

GnomAD3 exomes AF: 0.238 AC: 59310 AN: 249082 Hom.: 8485 AF XY: 0.234 AC XY: 31602 AN XY: 134818

Gnomad AFR exome AF: 0.611

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.149

Gnomad SAS exome AF: 0.228

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.232 AC: 337360 AN: 1452758 Hom.: 42254 Cov.: 34 AF XY: 0.230 AC XY: 166098 AN XY: 720968

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.329 AC: 50159 AN: 152230 Hom.: 10566 Cov.: 33 AF XY: 0.326 AC XY: 24284 AN XY: 74432

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.295

Alfa AF: 0.236 Hom.: 9367

Bravo AF: 0.339

TwinsUK AF: 0.221 AC: 819

ALSPAC AF: 0.231 AC: 892

ESP6500AA AF: 0.599 AC: 2639

ESP6500EA AF: 0.223 AC: 1919

ExAC AF: 0.249 AC: 30260

Asia WGS AF: 0.249 AC: 864 AN: 3478

EpiCase AF: 0.229

EpiControl AF: 0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.000031	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	0.69	P
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.0	D
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.11
ClinPred		0.032	T
GERP RS		2.5
Varity_R		0.31
gMVP		0.71

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

Other links and lift over

dbSNP: rs1122326; hg19: chr17-40274873; COSMIC: COSV56789691; COSMIC: COSV56789691;