20-3745047-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_052970.5(HSPA12B):​c.412C>T​(p.Leu138Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

HSPA12B
NM_052970.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33124265).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HSPA12BNM_052970.5 linkuse as main transcriptc.412C>T p.Leu138Phe 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.412C>T p.Leu138Phe missense_variant 5/131 NM_052970.5 ENSP00000254963 P1
HSPA12BENST00000399701.1 linkuse as main transcriptc.154C>T p.Leu52Phe missense_variant 4/121 ENSP00000382608

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152164
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 07, 2022The c.412C>T (p.L138F) alteration is located in exon 5 (coding exon 4) of the HSPA12B gene. This alteration results from a C to T substitution at nucleotide position 412, causing the leucine (L) at amino acid position 138 to be replaced by a phenylalanine (F). 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
Benign
0.12
BayesDel_addAF
Benign
-0.068
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.014
T;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.41
N;N
REVEL
Benign
0.14
Sift
Benign
0.081
T;T
Sift4G
Benign
0.11
T;T
Polyphen
0.99
D;.
Vest4
0.33
MutPred
0.57
Loss of helix (P = 0.0017);.;
MVP
0.55
MPC
0.95
ClinPred
0.74
D
GERP RS
4.4
Varity_R
0.22
gMVP
0.44

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: rs1162808467; hg19: chr20-3725694; API