17-42122906-C-A

Variant names:

• chr17-42122906-C-A
• NM_033194.3:c.56C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033194.3(HSPB9):​c.56C>A​(p.Pro19His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPB9 NM_033194.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27

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]

ENSG00000267261 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29148167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPB9	NM_033194.3	c.56C>A	p.Pro19His	missense_variant	Exon 1 of 1	ENST00000565659.2	NP_149971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPB9	ENST00000565659.2	c.56C>A	p.Pro19His	missense_variant	Exon 1 of 1	6	NM_033194.3	ENSP00000458018.1
ENSG00000267261	ENST00000592574.1	c.442-2077G>T		intron_variant	Intron 4 of 7	5		ENSP00000468367.1
ENSG00000267261	ENST00000585562.5	n.*158-2077G>T		intron_variant	Intron 1 of 4	3		ENSP00000464838.1
ENSG00000267261	ENST00000592248.5	n.442-2536G>T		intron_variant	Intron 3 of 4	3		ENSP00000468275.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461338 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726896

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.56C>A (p.P19H) alteration is located in exon 1 (coding exon 1) of the HSPB9 gene. This alteration results from a C to A substitution at nucleotide position 56, causing the proline (P) at amino acid position 19 to be replaced by a histidine (H). 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	0.19
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.036	D
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.6	D
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.39		Gain of MoRF binding (P = 0.0619);
MVP		0.89
ClinPred		0.98	D
GERP RS		3.5
Varity_R		0.25
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-40274924;