4-48081868-C-T

Position:

• chr4-48081868-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003328.3(TXK):​c.957-1740G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,082 control chromosomes in the GnomAD database, including 8,783 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8783 hom., cov: 31)
• Consequence: TXK NM_003328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

Genes affected

TXK (HGNC:12434): (TXK tyrosine kinase) Predicted to enable non-membrane spanning protein tyrosine kinase activity. Involved in positive regulation of interferon-gamma-mediated signaling pathway; positive regulation of macromolecule metabolic process; and protein autophosphorylation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXK	NM_003328.3	c.957-1740G>A		intron_variant		ENST00000264316.9	NP_003319.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXK	ENST00000264316.9	c.957-1740G>A		intron_variant		1	NM_003328.3	ENSP00000264316.4
TXK	ENST00000506073.2	c.957-1740G>A		intron_variant		3		ENSP00000422798.2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47276 AN: 151964 Hom.: 8783 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.0781

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.311 AC: 47281 AN: 152082 Hom.: 8783 Cov.: 31 AF XY: 0.309 AC XY: 22957 AN XY: 74322

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.0777

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.331

Alfa AF: 0.339 Hom.: 1800

Bravo AF: 0.306

Asia WGS AF: 0.165 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs7679010; hg19: chr4-48083885;