rs2289743

Variant names:

• chr15-41568500-C-G
• rs2289743
• NM_006293.4:c.1107+138C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006293.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRO3	NM_006293.4	MANE Select	c.1107+138C>G		intron	N/A	NP_006284.2
	TYRO3	NM_001330264.2		c.972+138C>G		intron	N/A	NP_001317193.1	H0YNK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRO3	ENST00000263798.8	TSL:1 MANE Select	c.1107+138C>G		intron	N/A	ENSP00000263798.3	Q06418
	TYRO3	ENST00000869540.1		c.1107+138C>G		intron	N/A	ENSP00000539599.1
	TYRO3	ENST00000869541.1		c.1107+138C>G		intron	N/A	ENSP00000539600.1

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

African (AFR) AF: 0.194 AC: 3110 AN: 16068

American (AMR) AF: 0.392 AC: 7788 AN: 19850

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 5257 AN: 14768

East Asian (EAS) AF: 0.157 AC: 5080 AN: 32360

South Asian (SAS) AF: 0.269 AC: 12778 AN: 47514

European-Finnish (FIN) AF: 0.299 AC: 11588 AN: 38742

Middle Eastern (MID) AF: 0.257 AC: 842 AN: 3276

European-Non Finnish (NFE) AF: 0.277 AC: 126200 AN: 454854

Other (OTH) AF: 0.289 AC: 9479 AN: 32802

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

African (AFR) AF: 0.194 AC: 8059 AN: 41482

American (AMR) AF: 0.359 AC: 5487 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1273 AN: 3460

East Asian (EAS) AF: 0.162 AC: 834 AN: 5164

South Asian (SAS) AF: 0.285 AC: 1366 AN: 4796

European-Finnish (FIN) AF: 0.293 AC: 3099 AN: 10560

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20015 AN: 67962

Other (OTH) AF: 0.275 AC: 579 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.0
DANN	Benign	0.48
PhyloP100		0.71
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: rs2289743; hg19: chr15-41860698;