Variant chr2-73830957-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_213622.4(STAMBP):c.101G>A(p.Arg34His) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

STAMBP
NM_213622.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.54

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]

STAMBP links:

STAMBP (HGNC:):

STAMBP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a region_of_interest Interaction with CHMP3 (size 126) in uniprot entity STABP_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_213622.4

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26394033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAMBP	NM_213622.4 linkuse as main transcript	c.101G>A	p.Arg34His	missense_variant	2/10	ENST00000394070.7	NP_998787.1	O95630-1A0A140VK54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAMBP	ENST00000394070.7 linkuse as main transcript	c.101G>A	p.Arg34His	missense_variant	2/10	1	NM_213622.4	ENSP00000377633.2		O95630-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251490

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 10, 2024

The c.101G>A (p.R34H) alteration is located in exon 2 (coding exon 1) of the STAMBP gene. This alteration results from a G to A substitution at nucleotide position 101, causing the arginine (R) at amino acid position 34 to be replaced by a histidine (H). 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

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.72

D;D;.;.;D;.;D;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.086

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.95

.;D;D;D;.;D;.;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.26

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

M;M;.;.;M;.;M;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0030

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.024

D;D;D;T;D;D;D;D

Polyphen

0.82

P;P;.;.;P;.;P;.

Vest4

0.76

MutPred

0.47

Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);

MVP

0.69

MPC

1.1

ClinPred

0.88

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.70

gMVP

0.55

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