22-40844874-C-T

Variant summary

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

The NM_003932.5(ST13):​c.280G>A​(p.Asp94Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D94E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ST13
NM_003932.5 missense

Scores

8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25
Variant links:
Genes affected
ST13 (HGNC:11343): (ST13 Hsp70 interacting protein) The protein encoded by this gene is an adaptor protein that mediates the association of the heat shock proteins HSP70 and HSP90. This protein has been shown to be involved in the assembly process of glucocorticoid receptor, which requires the assistance of multiple molecular chaperones. The expression of this gene is reported to be downregulated in colorectal carcinoma tissue suggesting that it is a candidate tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

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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=0.3360868).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ST13NM_003932.5 linkc.280G>A p.Asp94Asn missense_variant Exon 4 of 12 ENST00000216218.8 NP_003923.2 P50502Q0IJ56A0A140VKA6
ST13NM_001278589.2 linkc.250G>A p.Asp84Asn missense_variant Exon 4 of 12 NP_001265518.1 B4E0U6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ST13ENST00000216218.8 linkc.280G>A p.Asp94Asn missense_variant Exon 4 of 12 1 NM_003932.5 ENSP00000216218.3 P50502

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 17, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.280G>A (p.D94N) alteration is located in exon 4 (coding exon 4) of the ST13 gene. This alteration results from a G to A substitution at nucleotide position 280, causing the aspartic acid (D) at amino acid position 94 to be replaced by an asparagine (N). 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
0.32
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T;T;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.85
D;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.34
T;T;T
MetaSVM
Uncertain
-0.22
T
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-4.2
D;.;D
REVEL
Benign
0.25
Sift
Uncertain
0.0050
D;.;D
Sift4G
Benign
0.095
T;D;.
Polyphen
1.0
D;.;.
Vest4
0.50
MutPred
0.21
Gain of glycosylation at T93 (P = 0.1144);Gain of glycosylation at T93 (P = 0.1144);.;
MVP
0.68
MPC
0.37
ClinPred
1.0
D
GERP RS
5.9
Varity_R
0.31
gMVP
0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-41240878; API