15-41564269-A-ACACTGCCTGCAGCCCCCTTCAACATCACC

Position:

• chr15-41564269-A-ACACTGCCTGCAGCCCCCTTCAACATCACC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006293.4(TYRO3):​c.666_667insCACTGCCTGCAGCCCCCTTCAACATCACC​(p.Ala223HisfsTer21) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TYRO3 NM_006293.4 frameshift, splice_region
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 8.34

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRO3	NM_006293.4	c.666_667insCACTGCCTGCAGCCCCCTTCAACATCACC	p.Ala223HisfsTer21	frameshift_variant, splice_region_variant	5/19	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2	c.531_532insCACTGCCTGCAGCCCCCTTCAACATCACC	p.Ala178HisfsTer21	frameshift_variant, splice_region_variant	5/19		NP_001317193.1
TYRO3	XM_017022543.3	c.666_667insCACTGCCTGCAGCCCCCTTCAACATCACC	p.Ala223HisfsTer21	frameshift_variant, splice_region_variant	5/19		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8	c.666_667insCACTGCCTGCAGCCCCCTTCAACATCACC	p.Ala223HisfsTer21	frameshift_variant, splice_region_variant	5/19	1	NM_006293.4	ENSP00000263798	A2
TYRO3	ENST00000559066.5	c.531_532insCACTGCCTGCAGCCCCCTTCAACATCACC	p.Ala178HisfsTer21	frameshift_variant, splice_region_variant	5/19	5		ENSP00000454050	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

46,XX disorder of sex development Uncertain:1

Uncertain significance, no assertion criteria provided

research

Department for BioMedical Research, Inselspital, Bern University Hospital, University of Bern

Jan 01, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-41856467;