dbSNP rs766580482: STAMBP:p.Ser236Tyr (chr2-73847718-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM5

The NM_213622.4(STAMBP):c.707C>A(p.Ser236Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S236F) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

STAMBP
NM_213622.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.86

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

microcephaly-capillary malformation syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

STAMBP links:

ENSG00000286244 (HGNC:):

ENSG00000286244 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr2-73847718-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 492960.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213622.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STAMBP	NM_213622.4	MANE Select	c.707C>A	p.Ser236Tyr	missense	Exon 5 of 10	NP_998787.1
STAMBP	NM_001353967.2		c.707C>A	p.Ser236Tyr	missense	Exon 6 of 11	NP_001340896.1
STAMBP	NM_001353968.2		c.707C>A	p.Ser236Tyr	missense	Exon 5 of 10	NP_001340897.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STAMBP	ENST00000394070.7	TSL:1 MANE Select	c.707C>A	p.Ser236Tyr	missense	Exon 5 of 10	ENSP00000377633.2
STAMBP	ENST00000394073.6	TSL:1	c.707C>A	p.Ser236Tyr	missense	Exon 6 of 11	ENSP00000377636.1
STAMBP	ENST00000683877.1		c.707C>A	p.Ser236Tyr	missense	Exon 6 of 11	ENSP00000507446.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

6.9

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.24

Sift

Benign

0.045

Sift4G

Uncertain

0.0040

Polyphen

0.98

Vest4

0.48

MutPred

0.35

Loss of disorder (P = 0.0017)

MVP

0.60

MPC

1.2

ClinPred

0.98

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.55

gMVP

0.81

Mutation Taster

=6/94

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.36

Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over