11-123057914-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006597.6(HSPA8):c.1761T>C(p.Ala587=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,603,014 control chromosomes in the GnomAD database, including 65,838 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (10232 hom., cov: 32)
  • Exomes 𝑓: 0.26 (55606 hom.)
• Consequence: HSPA8 NM_006597.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

HSPA8 (HGNC:5241): (heat shock protein family A (Hsp70) member 8) This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-1.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA8	NM_006597.6	c.1761T>C	p.Ala587=	synonymous_variant	9/9	ENST00000534624.6
HSPA8	XM_011542798.2	c.1761T>C	p.Ala587=	synonymous_variant	9/9
HSPA8	NM_153201.4	c.1388-86T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA8	ENST00000534624.6	c.1761T>C	p.Ala587=	synonymous_variant	9/9	1	NM_006597.6	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52040 AN: 151842 Hom.: 10200 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.305

GnomAD3 exomes AF: 0.323 AC: 78283 AN: 242580 Hom.: 14604 AF XY: 0.313 AC XY: 41116 AN XY: 131310

Gnomad AFR exome AF: 0.529

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.583

Gnomad SAS exome AF: 0.357

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.263 AC: 381611 AN: 1451054 Hom.: 55606 Cov.: 31 AF XY: 0.265 AC XY: 190957 AN XY: 721686

Gnomad4 AFR exome AF: 0.534

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.576

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.343 AC: 52131 AN: 151960 Hom.: 10232 Cov.: 32 AF XY: 0.348 AC XY: 25837 AN XY: 74268

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.305

Alfa AF: 0.263 Hom.: 1932

Bravo AF: 0.362

Asia WGS AF: 0.446 AC: 1548 AN: 3478

EpiCase AF: 0.237

EpiControl AF: 0.241

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.7
Dann	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs4802; hg19: chr11-122928622; COSMIC: COSV57082578; COSMIC: COSV57082578;