4-48067679-G-C

Variant names:

• chr4-48067679-G-C
• rs2230594
• NM_003328.3:c.1542C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003328.3(TXK):​c.1542C>G​(p.Ala514Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,611,770 control chromosomes in the GnomAD database, including 217,792 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 0.47 (17700 hom., cov: 31)
  • Exomes 𝑓: 0.52 (200092 hom.)
• Consequence: TXK NM_003328.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003328.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXK	NM_003328.3	MANE Select	c.1542C>G	p.Ala514Ala	synonymous	Exon 15 of 15	NP_003319.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXK	ENST00000264316.9	TSL:1 MANE Select	c.1542C>G	p.Ala514Ala	synonymous	Exon 15 of 15	ENSP00000264316.4
	TXK	ENST00000514937.5	TSL:1	n.*139C>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000422139.1
	TXK	ENST00000514937.5	TSL:1	n.*139C>G		3_prime_UTR	Exon 4 of 4	ENSP00000422139.1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71502 AN: 151862 Hom.: 17691 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.486

GnomAD2 exomes AF: 0.520 AC: 130473 AN: 250896 AF XY: 0.515

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.679

Gnomad ASJ exome AF: 0.484

Gnomad EAS exome AF: 0.426

Gnomad FIN exome AF: 0.571

Gnomad NFE exome AF: 0.526

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.520 AC: 758847 AN: 1459790 Hom.: 200092 Cov.: 47 AF XY: 0.517 AC XY: 375845 AN XY: 726328

African (AFR) AF: 0.304 AC: 10157 AN: 33432

American (AMR) AF: 0.664 AC: 29638 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 12657 AN: 26084

East Asian (EAS) AF: 0.450 AC: 17858 AN: 39672

South Asian (SAS) AF: 0.465 AC: 40077 AN: 86140

European-Finnish (FIN) AF: 0.568 AC: 30341 AN: 53390

Middle Eastern (MID) AF: 0.438 AC: 2524 AN: 5762

European-Non Finnish (NFE) AF: 0.527 AC: 585117 AN: 1110346

Other (OTH) AF: 0.505 AC: 30478 AN: 60342

GnomAD4 genome AF: 0.471 AC: 71537 AN: 151980 Hom.: 17700 Cov.: 31 AF XY: 0.472 AC XY: 35091 AN XY: 74270

African (AFR) AF: 0.313 AC: 12962 AN: 41438

American (AMR) AF: 0.589 AC: 8989 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1702 AN: 3462

East Asian (EAS) AF: 0.439 AC: 2266 AN: 5160

South Asian (SAS) AF: 0.456 AC: 2197 AN: 4818

European-Finnish (FIN) AF: 0.582 AC: 6137 AN: 10548

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35610 AN: 67976

Other (OTH) AF: 0.484 AC: 1022 AN: 2110

Alfa AF: 0.422 Hom.: 2108

Bravo AF: 0.467

Asia WGS AF: 0.432 AC: 1505 AN: 3478

EpiCase AF: 0.505

EpiControl AF: 0.504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.21
DANN	Benign	0.39
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs2230594; hg19: chr4-48069696; COSMIC: COSV51915905;