2-73830927-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_213622.4(STAMBP):​c.71C>T​(p.Ala24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A24A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

STAMBP
NM_213622.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.48
Variant links:
Genes affected
STAMBP (HGNC:16950): (STAM binding protein) Cytokine-mediated signal transduction in the JAK-STAT cascade requires the involvement of adaptor molecules. One such signal-transducing adaptor molecule contains an SH3 domain that is required for induction of MYC and cell growth. The protein encoded by this gene binds to the SH3 domain of the signal-transducing adaptor molecule, and plays a critical role in cytokine-mediated signaling for MYC induction and cell cycle progression. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1
In a region_of_interest Interaction with CHMP3 (size 126) in uniprot entity STABP_HUMAN there are 11 pathogenic changes around while only 1 benign (92%) in NM_213622.4
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056495756).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STAMBPNM_213622.4 linkuse as main transcriptc.71C>T p.Ala24Val missense_variant 2/10 ENST00000394070.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STAMBPENST00000394070.7 linkuse as main transcriptc.71C>T p.Ala24Val missense_variant 2/101 NM_213622.4 P4O95630-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251452
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000260
AC:
38
AN:
1461768
Hom.:
0
Cov.:
31
AF XY:
0.0000248
AC XY:
18
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.0000306
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.0000227
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 02, 2021The c.71C>T (p.A24V) alteration is located in exon 2 (coding exon 1) of the STAMBP gene. This alteration results from a C to T substitution at nucleotide position 71, causing the alanine (A) at amino acid position 24 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 07, 2023This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 24 of the STAMBP protein (p.Ala24Val). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with STAMBP-related conditions. ClinVar contains an entry for this variant (Variation ID: 1409709). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STAMBP protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.52
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Uncertain
0.59
D;D;.;.;D;.;D;.
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.81
.;T;T;T;.;T;.;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.056
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;L;.;.;L;.;L;.
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.6
N;N;N;N;N;N;N;N
REVEL
Benign
0.052
Sift
Benign
0.39
T;T;T;T;T;T;T;T
Sift4G
Benign
0.60
T;T;T;T;T;T;T;T
Polyphen
0.10
B;B;.;.;B;.;B;.
Vest4
0.21
MutPred
0.24
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
0.47
MPC
0.30
ClinPred
0.094
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.092
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1479389015; hg19: chr2-74058054; COSMIC: COSV100277841; API