chr4-48138693-T-C

Variant names:

• chr4-48138693-T-C
• rs960602007
• NM_003215.3:c.1784A>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003215.3(TEC):​c.1784A>G​(p.Tyr595Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TEC NM_003215.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03
• Publications: 0 publications found

Genes affected

TEC (HGNC:11719): (tec protein tyrosine kinase) The protein encoded by this gene belongs to the Tec family of non-receptor protein-tyrosine kinases containing a pleckstrin homology domain. Tec family kinases are involved in the intracellular signaling mechanisms of cytokine receptors, lymphocyte surface antigens, heterotrimeric G-protein coupled receptors, and integrin molecules. They are also key players in the regulation of the immune functions. Tec kinase is an integral component of T cell signaling and has a distinct role in T cell activation. This gene may be associated with myelodysplastic syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.988

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003215.3. 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
	TEC	NM_003215.3	MANE Select	c.1784A>G	p.Tyr595Cys	missense	Exon 17 of 18	NP_003206.2	P42680

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEC	ENST00000381501.8	TSL:1 MANE Select	c.1784A>G	p.Tyr595Cys	missense	Exon 17 of 18	ENSP00000370912.3	P42680
	TEC	ENST00000955076.1		c.1784A>G	p.Tyr595Cys	missense	Exon 18 of 19	ENSP00000625135.1
	TEC	ENST00000955077.1		c.1784A>G	p.Tyr595Cys	missense	Exon 18 of 19	ENSP00000625136.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.40
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		6.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-8.3	D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.79		Gain of glycosylation at Y595 (P = 0.0034)
MVP		0.93
MPC		1.2
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.95
gMVP		0.91
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs960602007; hg19: chr4-48140710;