rs2289743

Positions:

• chr15-41568500-C-G

Variant summary

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

The NM_006293.4(TYRO3):​c.1107+138C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 812,234 control chromosomes in the GnomAD database, including 32,633 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 0.27 (5846 hom., cov: 30)
  • Exomes 𝑓: 0.28 (26787 hom.)
• Consequence: TYRO3 NM_006293.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRO3	NM_006293.4	c.1107+138C>G		intron_variant		ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2	c.972+138C>G		intron_variant			NP_001317193.1
TYRO3	XM_017022543.3	c.1107+138C>G		intron_variant			XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8	c.1107+138C>G		intron_variant		1	NM_006293.4	ENSP00000263798	A2
TYRO3	ENST00000559066.5	c.972+138C>G		intron_variant		5		ENSP00000454050	P4
TYRO3	ENST00000559815.1	c.305+138C>G		intron_variant, NMD_transcript_variant		5		ENSP00000453835

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41035 AN: 151880 Hom.: 5839 Cov.: 30

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.276 AC: 182122 AN: 660234 Hom.: 26787 AF XY: 0.277 AC XY: 93204 AN XY: 336998

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.356

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.270 AC: 41050 AN: 152000 Hom.: 5846 Cov.: 30 AF XY: 0.270 AC XY: 20056 AN XY: 74272

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.275

Alfa AF: 0.288 Hom.: 808

Bravo AF: 0.273

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.0
DANN	Benign	0.48

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: rs2289743; hg19: chr15-41860698;