chr20-3744945-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_052970.5(HSPA12B):ā€‹c.310C>Gā€‹(p.Pro104Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

HSPA12B
NM_052970.5 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HSPA12BNM_052970.5 linkuse as main transcriptc.310C>G p.Pro104Ala missense_variant 5/13 ENST00000254963.7 NP_443202.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HSPA12BENST00000254963.7 linkuse as main transcriptc.310C>G p.Pro104Ala missense_variant 5/131 NM_052970.5 ENSP00000254963 P1
HSPA12BENST00000399701.1 linkuse as main transcriptc.52C>G p.Pro18Ala missense_variant 4/121 ENSP00000382608

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250202
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135412
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461400
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727020
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

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 submitterclinical testingAmbry GeneticsSep 26, 2023The c.310C>G (p.P104A) alteration is located in exon 5 (coding exon 4) of the HSPA12B gene. This alteration results from a C to G substitution at nucleotide position 310, causing the proline (P) at amino acid position 104 to be replaced by an alanine (A). 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
0.55
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
T;T
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Benign
0.016
T
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.5
M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-6.8
D;D
REVEL
Uncertain
0.45
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
1.0
D;.
Vest4
0.94
MutPred
0.69
Loss of glycosylation at P104 (P = 0.0463);.;
MVP
0.72
MPC
1.8
ClinPred
0.99
D
GERP RS
4.4
Varity_R
0.56
gMVP
0.73

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.

Other links and lift over

dbSNP: rs374372742; hg19: chr20-3725592; API