rs74626772

Positions:

• chr1-16017882-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014424.5(HSPB7):​c.82T>C​(p.Ser28Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 36)
• Consequence: HSPB7 NM_014424.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

Genes affected

HSPB7 (HGNC:5249): (heat shock protein family B (small) member 7) This gene encodes a small heat shock family B member that can heterodimerize with similar heat shock proteins. Defects in this gene are associated with advanced heart failure. In addition, the encoded protein may be a tumor suppressor in the p53 pathway, with defects in this gene being associated with renal cell carcinoma. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPB7	NM_014424.5	c.82T>C	p.Ser28Pro	missense_variant	1/3	ENST00000311890.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPB7	ENST00000311890.14	c.82T>C	p.Ser28Pro	missense_variant	1/3	1	NM_014424.5	P3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	.;T;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.63	T;T;T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.50	T;T;T;T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.4	.;L;L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.38	N;N;N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Benign	0.070	T;T;T;T
Polyphen		0.68	.;P;.;.
Vest4		0.56
MutPred		0.17		Loss of phosphorylation at S28 (P = 9e-04);Loss of phosphorylation at S28 (P = 9e-04);Loss of phosphorylation at S28 (P = 9e-04);Loss of phosphorylation at S28 (P = 9e-04);
MVP		0.98
MPC		0.68
ClinPred		0.88	D
GERP RS		4.4
Varity_R		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs74626772; hg19: chr1-16344377;