chr17-42122906-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033194.3. 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
	HSPB9	NM_033194.3	MANE Select	c.56C>A	p.Pro19His	missense	Exon 1 of 1	NP_149971.1	Q9BQS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB9	ENST00000565659.2	TSL:6 MANE Select	c.56C>A	p.Pro19His	missense	Exon 1 of 1	ENSP00000458018.1	Q9BQS6
	ENSG00000267261	ENST00000592574.1	TSL:5	c.442-2077G>T		intron	N/A	ENSP00000468367.1	K7ERQ8
	ENSG00000267261	ENST00000585562.5	TSL:3	n.*158-2077G>T		intron	N/A	ENSP00000464838.1	K7EIP6

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

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111770

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.3
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
PromoterAI		0.0075	Neutral
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

Other links and lift over

hg19: chr17-40274924;