chr19-55274422-C-T

Variant names:

• chr19-55274422-C-T
• rs766830096
• NM_012267.5:c.616G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012267.5(HSPBP1):​c.616G>A​(p.Val206Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,293,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: HSPBP1 NM_012267.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69
• Publications: 0 publications found

Genes affected

HSPBP1 (HGNC:24989): (HSPA (Hsp70) binding protein 1) Enables ubiquitin protein ligase binding activity. Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process and positive regulation of protein ubiquitination. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17246494).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012267.5. 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
	HSPBP1	NM_012267.5	MANE Select	c.616G>A	p.Val206Ile	missense	Exon 4 of 8	NP_036399.3
	HSPBP1	NM_001297600.2		c.754G>A	p.Val252Ile	missense	Exon 3 of 7	NP_001284529.1
	HSPBP1	NM_001130106.2		c.616G>A	p.Val206Ile	missense	Exon 5 of 9	NP_001123578.1	Q9NZL4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPBP1	ENST00000433386.7	TSL:1 MANE Select	c.616G>A	p.Val206Ile	missense	Exon 4 of 8	ENSP00000398244.1	Q9NZL4-1
	HSPBP1	ENST00000255631.9	TSL:1	c.616G>A	p.Val206Ile	missense	Exon 5 of 9	ENSP00000255631.4	Q9NZL4-1
	HSPBP1	ENST00000587922.5	TSL:1	c.616G>A	p.Val206Ile	missense	Exon 3 of 7	ENSP00000467574.1	Q9NZL4-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000156 AC: 3 AN: 191812 AF XY: 0.0000189

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000240

Gnomad OTH exome AF: 0.000197

GnomAD4 exome AF: 0.0000101 AC: 13 AN: 1293330 Hom.: 0 Cov.: 36 AF XY: 0.0000109 AC XY: 7 AN XY: 640334

African (AFR) AF: 0.00 AC: 0 AN: 28996

American (AMR) AF: 0.00 AC: 0 AN: 37338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20890

East Asian (EAS) AF: 0.00 AC: 0 AN: 24720

South Asian (SAS) AF: 0.0000245 AC: 2 AN: 81510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29542

Middle Eastern (MID) AF: 0.00172 AC: 6 AN: 3480

European-Non Finnish (NFE) AF: 0.00000394 AC: 4 AN: 1016492

Other (OTH) AF: 0.0000199 AC: 1 AN: 50362

GnomAD4 genome Cov.: 30

Alfa AF: 0.000334 Hom.: 0

ExAC AF: 0.00000839 AC: 1

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	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.13
Sift	Benign	0.61	T
Sift4G	Benign	0.35	T
Vest4		0.25
MVP		0.25
MPC		0.29
ClinPred		0.14	T
GERP RS		5.6
Varity_R		0.13
gMVP		0.15
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs766830096; hg19: chr19-55785790;