6-31811171-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005527.4(HSPA1L):c.802G>A(p.Ala268Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,614,152 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 36 hom. )

Consequence

HSPA1L
NM_005527.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2O: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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01235792).

BP6

Variant 6-31811171-C-T is Benign according to our data. Variant chr6-31811171-C-T is described in ClinVar as [Benign]. Clinvar id is 372132.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00303 (4431/1461872) while in subpopulation SAS AF= 0.0229 (1973/86258). AF 95% confidence interval is 0.022. There are 36 homozygotes in gnomad4_exome. There are 2665 alleles in male gnomad4_exome subpopulation. Median coverage is 36. This position pass quality control queck.

BS2

High AC in GnomAd4 at 322 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA1L	NM_005527.4 link	c.802G>A	p.Ala268Thr	missense_variant	Exon 2 of 2	ENST00000375654.5	NP_005518.3	P34931A0A1U9X7W7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA1L	ENST00000375654.5 link	c.802G>A	p.Ala268Thr	missense_variant	Exon 2 of 2	1	NM_005527.4	ENSP00000364805.4		P34931

Frequencies

GnomAD3 genomes

AF:

0.00213

AC:

324

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0178

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00491

AC:

1233

AN:

251122

Hom.:

AF XY:

0.00603

AC XY:

819

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00963

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0239

Gnomad FIN exome

AF:

0.00249

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00303

AC:

4431

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00366

AC XY:

2665

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.0102

Gnomad4 EAS exome

AF:

0.00166

Gnomad4 SAS exome

AF:

0.0229

Gnomad4 FIN exome

AF:

0.00271

Gnomad4 NFE exome

AF:

0.00141

Gnomad4 OTH exome

AF:

0.00432

GnomAD4 genome

AF:

0.00211

AC:

322

AN:

152280

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0179

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00191

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.00180

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00501

AC:

608

EpiCase

AF:

0.00229

EpiControl

AF:

0.00255

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HSPA1L: BS1, BS2 -

HSPA1L-related disorder

Benign:1

Dec 28, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Inflammatory bowel disease 1

Other:1

Aug 06, 2016

Human Development and Health, University of Southampton

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

HSPA1L loss of function - Our results indicate that de novo and rare mutations in HSPA1L are associated with IBD and provide insights into the pathogenesis of IBD -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.089

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.7

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.024

Polyphen

1.0

Vest4

0.91

MVP

0.80

MPC

0.93

ClinPred

0.10

GERP RS

5.3

Varity_R

0.38

gMVP

0.18

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