NM_005546.4:c.1685G>T

Variant names:

• chr5-157248901-G-T
• NM_005546.4:c.1685G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005546.4(ITK):​c.1685G>T​(p.Arg562Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITK NM_005546.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72

Genes affected

ITK (HGNC:6171): (IL2 inducible T cell kinase) This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16383973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITK	NM_005546.4	c.1685G>T	p.Arg562Leu	missense_variant	Exon 16 of 17	ENST00000422843.8	NP_005537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITK	ENST00000422843.8	c.1685G>T	p.Arg562Leu	missense_variant	Exon 16 of 17	1	NM_005546.4	ENSP00000398655.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461664 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.43	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.18
Sift	Benign	0.72	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.44
MutPred		0.51		Loss of disorder (P = 0.0516);
MVP		0.81
MPC		0.49
ClinPred		0.77	D
GERP RS		4.8
Varity_R		0.46
gMVP		0.83

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-156675911;