Variant 1-161525250-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002155.5(HSPA6):c.592C>T(p.Leu198Phe) variant causes a missense change. The variant allele was found at a frequency of 0.111 in 1,613,694 control chromosomes in the GnomAD database, including 11,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.095 ( 923 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10513 hom. )

Consequence

HSPA6
NM_002155.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.09

Variant links:

Genes affected

HSPA6 (HGNC:5239): (heat shock protein family A (Hsp70) member 6) Enables enzyme binding activity; heat shock protein binding activity; and unfolded protein binding activity. Involved in cellular response to heat and protein refolding. Located in centriole and cytosol. Colocalizes with COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

HSPA6 links:

ENSG00000273112 (HGNC:):

ENSG00000273112 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020103753).

BP6

Variant 1-161525250-C-T is Benign according to our data. Variant chr1-161525250-C-T is described in ClinVar as [Benign]. Clinvar id is 1234232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA6	NM_002155.5 linkuse as main transcript	c.592C>T	p.Leu198Phe	missense_variant	1/1	ENST00000309758.6	NP_002146.2	P17066A0A384NKX5B3KSM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA6	ENST00000309758.6 linkuse as main transcript	c.592C>T	p.Leu198Phe	missense_variant	1/1	6	NM_002155.5	ENSP00000310219.4		P17066
ENSG00000273112	ENST00000537821.2 linkuse as main transcript	n.271+7113C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0949

AC:

14420

AN:

152008

Hom.:

923

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0376

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.0996

Gnomad FIN

AF:

0.0665

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.118

AC:

29640

AN:

250810

Hom.:

2181

AF XY:

0.118

AC XY:

15983

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.0365

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.262

Gnomad SAS exome

AF:

0.0971

Gnomad FIN exome

AF:

0.0681

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.112

AC:

164317

AN:

1461568

Hom.:

10513

Cov.:

AF XY:

0.112

AC XY:

81762

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.0379

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.0934

Gnomad4 FIN exome

AF:

0.0684

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.0947

AC:

14411

AN:

152126

Hom.:

923

Cov.:

AF XY:

0.0939

AC XY:

6982

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0375

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.0995

Gnomad4 FIN

AF:

0.0665

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.111

Hom.:

349

Bravo

AF:

0.0965

ESP6500AA

AF:

0.0397

AC:

175

ESP6500EA

AF:

0.115

AC:

990

ExAC

AF:

0.116

AC:

14094

Asia WGS

AF:

0.165

AC:

572

AN:

3476

EpiCase

AF:

0.128

EpiControl

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 28, 2020	This variant is associated with the following publications: (PMID: 31640787) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.1

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.21

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.19

ClinPred

0.024

GERP RS

2.3

Varity_R

0.77

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