rs371899193

Variant names:

• chr19-35755783-C-A
• rs371899193
• NM_144617.3:c.310G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-35755783-C-A
• chr19-35755783-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144617.3(HSPB6):​c.310G>T​(p.Glu104*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPB6 NM_144617.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.310G>T	p.Glu104*	stop_gained	Exon 2 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.310G>T	p.Glu104*	stop_gained	Exon 2 of 3	ENSP00000004982.3	O14558
	HSPB6	ENST00000587965.1	TSL:2	c.310G>T	p.Glu104*	stop_gained	Exon 2 of 2	ENSP00000467169.1	K7EP04
	HSPB6	ENST00000592984.6	TSL:4	c.310G>T	p.Glu104*	stop_gained	Exon 3 of 4	ENSP00000468057.2	A0A1X7SC65

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1434984 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 711728

African (AFR) AF: 0.00 AC: 0 AN: 32296

American (AMR) AF: 0.00 AC: 0 AN: 41766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25540

East Asian (EAS) AF: 0.00 AC: 0 AN: 37894

South Asian (SAS) AF: 0.00 AC: 0 AN: 82254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5110

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100476

Other (OTH) AF: 0.00 AC: 0 AN: 59126

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	41
DANN	Uncertain	0.99
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Benign	0.75	D
PhyloP100		1.9
Vest4		0.84
GERP RS		4.4
Mutation Taster		=14/186	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

dbSNP: rs371899193; hg19: chr19-36246684;