chr19-35755623-C-T

Variant names:

• chr19-35755623-C-T
• NM_144617.3:c.382G>A

Variant summary

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

The NM_144617.3(HSPB6):​c.382G>A​(p.Asp128Asn) 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: HSPB6 NM_144617.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75

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]

ENSG00000267328 (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=0.343293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPB6	NM_144617.3	c.382G>A	p.Asp128Asn	missense_variant	Exon 3 of 3	ENST00000004982.6	NP_653218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPB6	ENST00000004982.6	c.382G>A	p.Asp128Asn	missense_variant	Exon 3 of 3	1	NM_144617.3	ENSP00000004982.3
HSPB6	ENST00000587965	c.*56G>A		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000467169.1
HSPB6	ENST00000592984.6	c.*16G>A		downstream_gene_variant		4		ENSP00000468057.2
ENSG00000267328	ENST00000587767.1	n.*133C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1381460 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 681732

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

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.382G>A (p.D128N) alteration is located in exon 3 (coding exon 3) of the HSPB6 gene. This alteration results from a G to A substitution at nucleotide position 382, causing the aspartic acid (D) at amino acid position 128 to be replaced by an asparagine (N). 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	Benign	0.0039	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.075
Eigen_PC	Benign	0.068
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.33
Sift	Benign	0.11	T
Sift4G	Benign	0.20	T
Polyphen		0.098	B
Vest4		0.35
MutPred		0.57		Gain of MoRF binding (P = 0.0523);
MVP		1.0
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.48
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36246524;