rs543420319

Variant names:

• chr4-48149610-T-G
• rs543420319
• NM_003215.3:c.953A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-48149610-T-G
• chr4-48149610-T-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.953A>C​(p.His318Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,156 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TEC NM_003215.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.19
• 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: 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, 0.873

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.953A>C	p.His318Pro	missense	Exon 11 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.953A>C	p.His318Pro	missense	Exon 11 of 18	ENSP00000370912.3	P42680
	TEC	ENST00000955076.1		c.953A>C	p.His318Pro	missense	Exon 12 of 19	ENSP00000625135.1
	TEC	ENST00000955077.1		c.953A>C	p.His318Pro	missense	Exon 12 of 19	ENSP00000625136.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000802 AC: 2 AN: 249474 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460156 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726410

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 44340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39500

South Asian (SAS) AF: 0.00 AC: 0 AN: 85952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111434

Other (OTH) AF: 0.00 AC: 0 AN: 60330

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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Benign	0.97
DEOGEN2	Pathogenic	0.86	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.2
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-8.0	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.39		Gain of glycosylation at Y313 (P = 0.0449)
MVP		0.92
MPC		1.4
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.95
gMVP		0.89
Mutation Taster		=40/60	disease causing

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: rs543420319; hg19: chr4-48151627;