chr2-73860105-G-C

Variant names:

• chr2-73860105-G-C
• rs181632285
• NM_213622.4:c.1172G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_213622.4(STAMBP):​c.1172G>C​(p.Arg391Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R391H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAMBP NM_213622.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04
• Publications: 2 publications found

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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAMBP	NM_213622.4	MANE Select	c.1172G>C	p.Arg391Pro	missense	Exon 9 of 10	NP_998787.1	O95630-1
	STAMBP	NM_001353967.2		c.1172G>C	p.Arg391Pro	missense	Exon 10 of 11	NP_001340896.1	A0A140VK54
	STAMBP	NM_001353968.2		c.1172G>C	p.Arg391Pro	missense	Exon 9 of 10	NP_001340897.1	A0A140VK54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAMBP	ENST00000394070.7	TSL:1 MANE Select	c.1172G>C	p.Arg391Pro	missense	Exon 9 of 10	ENSP00000377633.2	O95630-1
	STAMBP	ENST00000394073.6	TSL:1	c.1172G>C	p.Arg391Pro	missense	Exon 10 of 11	ENSP00000377636.1	O95630-1
	STAMBP	ENST00000683877.1		c.1205G>C	p.Arg402Pro	missense	Exon 10 of 11	ENSP00000507446.1	A0A804HJC8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.0074	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.93	L
PhyloP100		5.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.61
MutPred		0.30		Gain of sheet (P = 0.0221)
MVP		0.45
MPC		1.1
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.92
gMVP		0.81
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs181632285; hg19: chr2-74087232;