rs2277537

chr15-41564882-A-G

Variant summary

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

The NM_006293.4(TYRO3):c.668-144A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 637,230 control chromosomes in the GnomAD database, including 71,051 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 0.48 (18959 hom., cov: 32)
  • Exomes 𝑓: 0.45 (52092 hom.)
• Consequence: TYRO3 NM_006293.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYRO3	NM_006293.4	c.668-144A>G		intron_variant		ENST00000263798.8
TYRO3	NM_001330264.2	c.533-144A>G		intron_variant
TYRO3	XM_017022543.3	c.668-144A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYRO3	ENST00000263798.8	c.668-144A>G		intron_variant		1	NM_006293.4	A2
TYRO3	ENST00000559066.5	c.533-144A>G		intron_variant		5		P4
TYRO3	ENST00000560227.1	n.99A>G		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73449 AN: 151820 Hom.: 18932 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.448 AC: 217608 AN: 485292 Hom.: 52092 Cov.: 4 AF XY: 0.448 AC XY: 115232 AN XY: 257174

Gnomad4 AFR exome AF: 0.630

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.831

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.433

GnomAD4 genome AF: 0.484 AC: 73532 AN: 151938 Hom.: 18959 Cov.: 32 AF XY: 0.484 AC XY: 35918 AN XY: 74254

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.460

Alfa AF: 0.413 Hom.: 13022

Bravo AF: 0.496

Asia WGS AF: 0.626 AC: 2175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.89
Dann	Benign	0.46

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: rs2277537; hg19: chr15-41857080;