Variant chr2-197501064-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002157.3(HSPE1):c.4-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,602,078 control chromosomes in the GnomAD database, including 24,327 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 0.15 ( 1897 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22430 hom. )

Consequence

HSPE1
NM_002157.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008184

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.316

Variant links:

Genes affected

HSPE1 (HGNC:5269): (heat shock protein family E (Hsp10) member 1) This gene encodes a major heat shock protein which functions as a chaperonin. Its structure consists of a heptameric ring which binds to another heat shock protein in order to form a symmetric, functional heterodimer which enhances protein folding in an ATP-dependent manner. This gene and its co-chaperonin, HSPD1, are arranged in a head-to-head orientation on chromosome 2. Naturally occurring read-through transcription occurs between this locus and the neighboring locus MOBKL3.[provided by RefSeq, Feb 2011]

HSPE1 links:

HSPE1-MOB4 (HGNC:):

HSPE1-MOB4 links:

HSPD1 (HGNC:5261): (heat shock protein family D (Hsp60) member 1) This gene encodes a member of the chaperonin family. The encoded mitochondrial protein may function as a signaling molecule in the innate immune system. This protein is essential for the folding and assembly of newly imported proteins in the mitochondria. This gene is adjacent to a related family member and the region between the 2 genes functions as a bidirectional promoter. Several pseudogenes have been associated with this gene. Two transcript variants encoding the same protein have been identified for this gene. Mutations associated with this gene cause autosomal recessive spastic paraplegia 13. [provided by RefSeq, Jun 2010]

HSPD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPE1	NM_002157.3 linkuse as main transcript	c.4-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000233893.10
HSPE1-MOB4	NM_001202485.2 linkuse as main transcript	c.4-10C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPE1	ENST00000233893.10 linkuse as main transcript	c.4-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002157.3	P1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22251

AN:

152074

Hom.:

1894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0613

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.0925

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.167

AC:

41013

AN:

246078

Hom.:

3769

AF XY:

0.167

AC XY:

22188

AN XY:

133214

show subpopulations

Gnomad AFR exome

AF:

0.0572

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.234

Gnomad SAS exome

AF:

0.0900

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.173

AC:

250308

AN:

1449886

Hom.:

22430

Cov.:

AF XY:

0.171

AC XY:

123415

AN XY:

720836

show subpopulations

Gnomad4 AFR exome

AF:

0.0541

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.229

Gnomad4 SAS exome

AF:

0.0925

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.146

AC:

22262

AN:

152192

Hom.:

1897

Cov.:

AF XY:

0.148

AC XY:

10979

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0612

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.235

Gnomad4 EAS

AF:

0.230

Gnomad4 SAS

AF:

0.0943

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.162

Hom.:

879

Bravo

AF:

0.148

Asia WGS

AF:

0.138

AC:

481

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.7

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000082

dbscSNV1_RF

Benign

0.0080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over