rs12259

Positions:

• chr15-41579294-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006293.4(TYRO3):​c.*1018A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 151,946 control chromosomes in the GnomAD database, including 58 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 0.028 (58 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TYRO3 NM_006293.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73

Genes affected

TYRO3 (HGNC:12446): (TYRO3 protein tyrosine kinase) The gene is part of a 3-member transmembrane receptor kinase receptor family with a processed pseudogene distal on chromosome 15. The encoded protein is activated by the products of the growth arrest-specific gene 6 and protein S genes and is involved in controlling cell survival and proliferation, spermatogenesis, immunoregulation and phagocytosis. The encoded protein has also been identified as a cell entry factor for Ebola and Marburg viruses. [provided by RefSeq, May 2010]

TYRO3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0279 (4238/151946) while in subpopulation NFE AF= 0.0398 (2704/67990). AF 95% confidence interval is 0.0385. There are 58 homozygotes in gnomad4. There are 1917 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 58 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRO3	NM_006293.4	c.*1018A>G		3_prime_UTR_variant	19/19	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2	c.*1018A>G		3_prime_UTR_variant	19/19		NP_001317193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8	c.*1018A>G		3_prime_UTR_variant	19/19	1	NM_006293.4	ENSP00000263798.3
TYRO3	ENST00000568490.1	n.1960A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4239 AN: 151842 Hom.: 58 Cov.: 33

Gnomad AFR AF: 0.00782

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0880

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0422

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0279 AC: 4238 AN: 151946 Hom.: 58 Cov.: 33 AF XY: 0.0258 AC XY: 1917 AN XY: 74270

Gnomad4 AFR AF: 0.00780

Gnomad4 AMR AF: 0.0343

Gnomad4 ASJ AF: 0.0880

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0181

Gnomad4 NFE AF: 0.0398

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0329 Hom.: 7

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.61

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: rs12259; hg19: chr15-41871492;