22-40848367-T-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003932.5(ST13):c.171A>T(p.Glu57Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,608,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ST13
NM_003932.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.203

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]

ST13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09389594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST13	NM_003932.5 link	c.171A>T	p.Glu57Asp	missense_variant, splice_region_variant	Exon 3 of 12	ENST00000216218.8	NP_003923.2	P50502Q0IJ56A0A140VKA6
ST13	NM_001278589.2 link	c.169-28A>T		intron_variant	Intron 2 of 11		NP_001265518.1	B4E0U6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ST13	ENST00000216218.8 link	c.171A>T	p.Glu57Asp	missense_variant, splice_region_variant	Exon 3 of 12	1	NM_003932.5	ENSP00000216218.3	P50502
ST13	ENST00000411695.1 link	c.60A>T	p.Glu20Asp	missense_variant, splice_region_variant	Exon 3 of 8	5		ENSP00000392067.1	F6VDH7
ST13	ENST00000455824.1 link	n.111-3458A>T		intron_variant	Intron 1 of 8	5		ENSP00000397062.1	F8WAQ7

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000478

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1456634

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

724954

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000812

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

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:

0.000478

Bravo

AF:

0.000102

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.171A>T (p.E57D) alteration is located in exon 3 (coding exon 3) of the ST13 gene. This alteration results from a A to T substitution at nucleotide position 171, causing the glutamic acid (E) at amino acid position 57 to be replaced by an aspartic acid (D). 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

0.089

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.094

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

N;.;N

REVEL

Benign

0.065

Sift

Benign

0.31

T;.;T

Sift4G

Benign

0.25

T;T;.

Polyphen

0.067

B;.;.

Vest4

0.31

MutPred

0.22

Loss of methylation at K59 (P = 0.1048);Loss of methylation at K59 (P = 0.1048);.;

MVP

0.61

MPC

0.33

ClinPred

0.33

GERP RS

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.099

gMVP

0.052

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