chr15-41564269-A-ACACTGCCTGCAGCCCCCTTCAACATCACC

Variant names:

• chr15-41564269-A-ACACTGCCTGCAGCCCCCTTCAACATCACC
• NM_006293.4:c.666_667insCACTGCCTGCAGCCCCCTTCAACATCACC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.666_667insCACTGCCTGCAGCCCCCTTCAACATCACC	p.Ala223HisfsTer21	frameshift splice_region	Exon 5 of 19	NP_006284.2
	TYRO3	NM_001330264.2		c.531_532insCACTGCCTGCAGCCCCCTTCAACATCACC	p.Ala178HisfsTer21	frameshift splice_region	Exon 5 of 19	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.666_667insCACTGCCTGCAGCCCCCTTCAACATCACC	p.Ala223HisfsTer21	frameshift splice_region	Exon 5 of 19	ENSP00000263798.3	Q06418
	TYRO3	ENST00000869540.1		c.666_667insCACTGCCTGCAGCCCCCTTCAACATCACC	p.Ala223HisfsTer21	frameshift splice_region	Exon 5 of 20	ENSP00000539599.1
	TYRO3	ENST00000869541.1		c.666_667insCACTGCCTGCAGCCCCCTTCAACATCACC	p.Ala223HisfsTer21	frameshift splice_region	Exon 5 of 20	ENSP00000539600.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	46,XX disorder of sex development (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.3

Splicing

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

Other links and lift over

hg19: chr15-41856467;