rs397514697

Positions:

chr2-73845186-T-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP5_Moderate

The NM_213622.4(STAMBP):c.299T>A(p.Phe100Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

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

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

STAMBP
NM_213622.4 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.32

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a region_of_interest Interaction with CHMP3 (size 126) in uniprot entity STABP_HUMAN there are 10 pathogenic changes around while only 1 benign (91%) in NM_213622.4

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-73845186-T-A is Pathogenic according to our data. Variant chr2-73845186-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 50796.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-73845186-T-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAMBP	NM_213622.4 linkuse as main transcript	c.299T>A	p.Phe100Tyr	missense_variant	4/10	ENST00000394070.7
LOC112268419	XR_007087106.1 linkuse as main transcript	n.358-6284A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAMBP	ENST00000394070.7 linkuse as main transcript	c.299T>A	p.Phe100Tyr	missense_variant	4/10	1	NM_213622.4	P4	O95630-1
	ENST00000650890.1 linkuse as main transcript	n.346-6284A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251028

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000151

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000198

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Microcephaly-capillary malformation syndrome

Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Baylor Genetics	Sep 01, 2017	This variant has been previously reported as disease-causing and was found once in our laboratory in trans with a nonsense variant [D252X] in a 1-month-old male with hypotonia, spasticity, seizures, microcephaly, infarction of left hemisphere globus pallidus and dural venous sinus thrombosis, bradycaridia, hypoplastic nail, rash, and mild thrombocytopenia -
Pathogenic, no assertion criteria provided	literature only	OMIM	May 01, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.81

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

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

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

M_CAP

Pathogenic

0.36

MetaRNN

Uncertain

0.58

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

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

2.9

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

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-2.3

N;N;N;N;N;N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0040

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

Sift4G

Uncertain

0.0070

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

Polyphen

1.0

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

Vest4

0.85

MutPred

0.32

Loss of methylation at K102 (P = 0.0634);Loss of methylation at K102 (P = 0.0634);Loss of methylation at K102 (P = 0.0634);Loss of methylation at K102 (P = 0.0634);Loss of methylation at K102 (P = 0.0634);Loss of methylation at K102 (P = 0.0634);Loss of methylation at K102 (P = 0.0634);Loss of methylation at K102 (P = 0.0634);

MVP

0.61

MPC

1.0

ClinPred

0.92

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.89

gMVP

0.50

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