Variant 6-31810169-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005527.4(HSPA1L):c.1804G>A(p.Glu602Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,526,028 control chromosomes in the GnomAD database, including 78,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.26 ( 6366 hom., cov: 32)

Exomes 𝑓: 0.32 ( 72131 hom. )

Consequence

HSPA1L
NM_005527.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

HSPA1L (HGNC:5234): (heat shock protein family A (Hsp70) member 1 like) This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein. [provided by RefSeq, Jul 2008]

HSPA1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037553012).

BP6

Variant 6-31810169-C-T is Benign according to our data. Variant chr6-31810169-C-T is described in ClinVar as [Benign]. Clinvar id is 3059263.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA1L	NM_005527.4 linkuse as main transcript	c.1804G>A	p.Glu602Lys	missense_variant	2/2	ENST00000375654.5	NP_005518.3	P34931A0A1U9X7W7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA1L	ENST00000375654.5 linkuse as main transcript	c.1804G>A	p.Glu602Lys	missense_variant	2/2	1	NM_005527.4	ENSP00000364805.4		P34931

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38959

AN:

151994

Hom.:

6360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0582

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.277

GnomAD3 exomes

AF:

0.322

AC:

57626

AN:

179186

Hom.:

10244

AF XY:

0.329

AC XY:

31032

AN XY:

94420

show subpopulations

Gnomad AFR exome

AF:

0.0499

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.494

Gnomad EAS exome

AF:

0.386

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.317

AC:

436075

AN:

1373916

Hom.:

72131

Cov.:

AF XY:

0.320

AC XY:

216215

AN XY:

675512

show subpopulations

Gnomad4 AFR exome

AF:

0.0446

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.498

Gnomad4 EAS exome

AF:

0.446

Gnomad4 SAS exome

AF:

0.310

Gnomad4 FIN exome

AF:

0.293

Gnomad4 NFE exome

AF:

0.318

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.256

AC:

38974

AN:

152112

Hom.:

6366

Cov.:

AF XY:

0.258

AC XY:

19212

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0581

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.381

Gnomad4 SAS

AF:

0.310

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.329

Hom.:

14548

Bravo

AF:

0.250

ESP6500AA

AF:

0.0651

AC:

287

ESP6500EA

AF:

0.329

AC:

2826

ExAC

AF:

0.316

AC:

37728

Asia WGS

AF:

0.309

AC:

1079

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HSPA1L-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.3

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.1

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.026

Polyphen

0.96

Vest4

0.26

MPC

0.91

ClinPred

0.027

GERP RS

5.9

Varity_R

0.26

gMVP

0.58

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over