4-48145429-A-G

Variant names:

• chr4-48145429-A-G
• rs868616029
• NM_003215.3:c.1232T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003215.3(TEC):​c.1232T>C​(p.Ile411Thr) 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: 32)
• Consequence: TEC NM_003215.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.9

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.1232T>C	p.Ile411Thr	missense	Exon 13 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.1232T>C	p.Ile411Thr	missense	Exon 13 of 18	ENSP00000370912.3	P42680
	TEC	ENST00000955076.1		c.1232T>C	p.Ile411Thr	missense	Exon 14 of 19	ENSP00000625135.1
	TEC	ENST00000955077.1		c.1232T>C	p.Ile411Thr	missense	Exon 14 of 19	ENSP00000625136.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250954 AF XY: 0.00000737

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome Cov.: 35

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	0.46
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	1.4	L
PhyloP100		5.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.74		Gain of disorder (P = 0.0115)
MVP		0.93
MPC		1.2
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.82
gMVP		0.60
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs868616029; hg19: chr4-48147446;