Variant chr20-3740898-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052970.5(HSPA12B):c.127C>A(p.Pro43Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000251 in 1,612,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

HSPA12B
NM_052970.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA12B	NM_052970.5 linkuse as main transcript	c.127C>A	p.Pro43Thr	missense_variant	3/13	ENST00000254963.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA12B	ENST00000254963.7 linkuse as main transcript	c.127C>A	p.Pro43Thr	missense_variant	3/13	1	NM_052970.5	P1
HSPA12B	ENST00000399701.1 linkuse as main transcript	c.-117-1386C>A		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000136

AC:

AN:

249142

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134756

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000285

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000262

AC:

383

AN:

1460618

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

208

AN XY:

726576

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000333

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000145

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000192

Hom.:

Bravo

AF:

0.000117

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000416

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.127C>A (p.P43T) alteration is located in exon 3 (coding exon 2) of the HSPA12B gene. This alteration results from a C to A substitution at nucleotide position 127, causing the proline (P) at amino acid position 43 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.3

REVEL

Benign

0.15

Sift

Uncertain

0.015

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.60

MVP

0.68

MPC

0.21

ClinPred

0.12

GERP RS

4.4

Varity_R

0.14

gMVP

0.42

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