Variant 20-3746017-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_052970.5(HSPA12B):c.661G>A(p.Glu221Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00978 in 1,613,750 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 9 hom., cov: 32)

Exomes 𝑓: 0.010 ( 86 hom. )

Consequence

HSPA12B
NM_052970.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.70

Variant links:

Genes affected

HSPA12B (HGNC:16193): (heat shock protein family A (Hsp70) member 12B) The protein encoded by this gene contains an atypical heat shock protein 70 (Hsp70) ATPase domain and is therefore a distant member of the mammalian Hsp70 family. This gene may be involved in susceptibility to atherosclerosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

HSPA12B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010157734).

BP6

Variant 20-3746017-G-A is Benign according to our data. Variant chr20-3746017-G-A is described in ClinVar as [Benign]. Clinvar id is 3387974.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA12B	NM_052970.5 linkuse as main transcript	c.661G>A	p.Glu221Lys	missense_variant	7/13	ENST00000254963.7	NP_443202.3	Q96MM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA12B	ENST00000254963.7 linkuse as main transcript	c.661G>A	p.Glu221Lys	missense_variant	7/13	1	NM_052970.5	ENSP00000254963.2		Q96MM6
HSPA12B	ENST00000399701.1 linkuse as main transcript	c.403G>A	p.Glu135Lys	missense_variant	6/12	1		ENSP00000382608.1		Q5JX83

Frequencies

GnomAD3 genomes

AF:

0.00727

AC:

1107

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00862

GnomAD3 exomes

AF:

0.00715

AC:

1794

AN:

251076

Hom.:

AF XY:

0.00721

AC XY:

979

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00882

Gnomad ASJ exome

AF:

0.00338

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0100

AC:

14682

AN:

1461392

Hom.:

Cov.:

AF XY:

0.00983

AC XY:

7147

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00857

Gnomad4 ASJ exome

AF:

0.00379

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00152

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00727

AC:

1107

AN:

152358

Hom.:

Cov.:

AF XY:

0.00679

AC XY:

506

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.00997

Hom.:

Bravo

AF:

0.00788

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0119

AC:

102

ExAC

AF:

0.00685

AC:

832

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00960

EpiControl

AF:

0.0126

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

HSPA12B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.066

Eigen_PC

Benign

0.066

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

D;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.14

Sift

Benign

0.11

T;T

Sift4G

Uncertain

0.017

D;D

Polyphen

0.070

B;.

Vest4

0.53

MVP

0.43

MPC

1.1

ClinPred

0.021

GERP RS

4.3

Varity_R

0.58

gMVP

0.75

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