6-31811171-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

14 publications found

Variant links:

COSMIC-nc: COSV108228950

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 372132.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 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 GnomAdExome4. There are 2665 alleles in the male GnomAdExome4 subpopulation. Median coverage is 36. This position passed quality control check.

BS2

High AC in GnomAd4 at 322 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005527.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA1L	NM_005527.4	MANE Select	c.802G>A	p.Ala268Thr	missense	Exon 2 of 2	NP_005518.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA1L	ENST00000375654.5	TSL:1 MANE Select	c.802G>A	p.Ala268Thr	missense	Exon 2 of 2	ENSP00000364805.4

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

GnomAD2 exomes

AF:

0.00491

AC:

1233

AN:

251122

AF XY:

0.00603

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 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

African (AFR)

AF:

0.000209

AC:

AN:

33480

American (AMR)

AF:

0.00230

AC:

103

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0102

AC:

267

AN:

26136

East Asian (EAS)

AF:

0.00166

AC:

AN:

39700

South Asian (SAS)

AF:

0.0229

AC:

1973

AN:

86258

European-Finnish (FIN)

AF:

0.00271

AC:

145

AN:

53410

Middle Eastern (MID)

AF:

0.00677

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00141

AC:

1570

AN:

1112008

Other (OTH)

AF:

0.00432

AC:

261

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

338

677

1015

1354

1692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00211

AC:

322

AN:

152280

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41556

American (AMR)

AF:

0.00203

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00950

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5178

South Asian (SAS)

AF:

0.0179

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00191

AC:

130

AN:

68016

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00184

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

Aug 01, 2025

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

(source)

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

PhyloP100

7.9

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

Mutation Taster

=46/54

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over