NM_003215.3:c.1499C>T

Variant names:

• chr4-48141391-G-A
• rs763650133
• NM_003215.3:c.1499C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003215.3(TEC):​c.1499C>T​(p.Ala500Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: TEC NM_003215.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15847778).

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.1499C>T	p.Ala500Val	missense	Exon 15 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.1499C>T	p.Ala500Val	missense	Exon 15 of 18	ENSP00000370912.3	P42680
	TEC	ENST00000955076.1		c.1499C>T	p.Ala500Val	missense	Exon 16 of 19	ENSP00000625135.1
	TEC	ENST00000955077.1		c.1499C>T	p.Ala500Val	missense	Exon 16 of 19	ENSP00000625136.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251108 AF XY: 0.0000147

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: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461492 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727048

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111884

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	Benign	0.097
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.89	L
PhyloP100		1.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.080
Sift	Benign	0.11	T
Sift4G	Benign	0.11	T
Polyphen		0.17	B
Vest4		0.20
MutPred		0.38		Gain of ubiquitination at K504 (P = 0.1375)
MVP		0.56
MPC		0.38
ClinPred		0.18	T
GERP RS		3.8
Varity_R		0.065
gMVP		0.32
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs763650133; hg19: chr4-48143408; COSMIC: COSV67406291;