Variant 6-31810495-G-A 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.1478C>T(p.Thr493Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 1,613,352 control chromosomes in the GnomAD database, including 566,847 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.88 ( 58821 hom., cov: 31)

Exomes 𝑓: 0.83 ( 508026 hom. )

Consequence

HSPA1L
NM_005527.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.346

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=6.9402125E-7).

BP6

Variant 6-31810495-G-A is Benign according to our data. Variant chr6-31810495-G-A is described in ClinVar as [Benign]. Clinvar id is 3060421.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 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.1478C>T	p.Thr493Met	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.1478C>T	p.Thr493Met	missense_variant	2/2	1	NM_005527.4	ENSP00000364805.4		P34931

Frequencies

GnomAD3 genomes

AF:

0.877

AC:

133293

AN:

152002

Hom.:

58760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.967

Gnomad AMI

AF:

0.768

Gnomad AMR

AF:

0.912

Gnomad ASJ

AF:

0.935

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.888

Gnomad FIN

AF:

0.845

Gnomad MID

AF:

0.943

Gnomad NFE

AF:

0.822

Gnomad OTH

AF:

0.903

GnomAD3 exomes

AF:

0.866

AC:

217175

AN:

250884

Hom.:

94552

AF XY:

0.864

AC XY:

117222

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.969

Gnomad AMR exome

AF:

0.940

Gnomad ASJ exome

AF:

0.938

Gnomad EAS exome

AF:

0.813

Gnomad SAS exome

AF:

0.891

Gnomad FIN exome

AF:

0.837

Gnomad NFE exome

AF:

0.829

Gnomad OTH exome

AF:

0.867

GnomAD4 exome

AF:

0.832

AC:

1216116

AN:

1461232

Hom.:

508026

Cov.:

AF XY:

0.835

AC XY:

606890

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.968

Gnomad4 AMR exome

AF:

0.935

Gnomad4 ASJ exome

AF:

0.934

Gnomad4 EAS exome

AF:

0.875

Gnomad4 SAS exome

AF:

0.890

Gnomad4 FIN exome

AF:

0.833

Gnomad4 NFE exome

AF:

0.815

Gnomad4 OTH exome

AF:

0.843

GnomAD4 genome

AF:

0.877

AC:

133414

AN:

152120

Hom.:

58821

Cov.:

AF XY:

0.878

AC XY:

65247

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.966

Gnomad4 AMR

AF:

0.912

Gnomad4 ASJ

AF:

0.935

Gnomad4 EAS

AF:

0.805

Gnomad4 SAS

AF:

0.888

Gnomad4 FIN

AF:

0.845

Gnomad4 NFE

AF:

0.822

Gnomad4 OTH

AF:

0.903

Alfa

AF:

0.844

Hom.:

114932

Bravo

AF:

0.886

TwinsUK

AF:

0.820

AC:

3040

ALSPAC

AF:

0.813

AC:

3135

ESP6500AA

AF:

0.962

AC:

4237

ESP6500EA

AF:

0.823

AC:

7079

ExAC

AF:

0.865

AC:

105038

Asia WGS

AF:

0.897

AC:

3122

AN:

3478

EpiCase

AF:

0.837

EpiControl

AF:

0.849

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 21, 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

Benign

0.064

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.0

DANN

Benign

0.92

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.25

MetaRNN

Benign

6.9e-7

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.93

PrimateAI

Benign

0.38

PROVEAN

Benign

0.22

REVEL

Benign

0.078

Sift

Benign

0.097

Sift4G

Benign

0.098

Polyphen

0.13

Vest4

0.035

MPC

0.29

ClinPred

0.0068

GERP RS

-4.2

Varity_R

0.038

gMVP

0.14

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