chr19-35755623-C-T

Variant names:

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

Variant summary

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

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

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=0.343293).

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.382G>A	p.Asp128Asn	missense	Exon 3 of 3	NP_653218.1	O14558

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB6	ENST00000004982.6	TSL:1 MANE Select	c.382G>A	p.Asp128Asn	missense	Exon 3 of 3	ENSP00000004982.3	O14558
	HSPB6	ENST00000906439.1		c.259G>A	p.Asp87Asn	missense	Exon 2 of 2	ENSP00000576498.1
	HSPB6	ENST00000587965.1	TSL:2	c.*56G>A		3_prime_UTR	Exon 2 of 2	ENSP00000467169.1	K7EP04

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

African (AFR) AF: 0.00 AC: 0 AN: 30702

American (AMR) AF: 0.00 AC: 0 AN: 35440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24944

East Asian (EAS) AF: 0.00 AC: 0 AN: 35214

South Asian (SAS) AF: 0.00 AC: 0 AN: 78570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076768

Other (OTH) AF: 0.00 AC: 0 AN: 57666

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	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
PhyloP100		1.8
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
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

hg19: chr19-36246524;