15-41570063-T-C

Position:

• chr15-41570063-T-C

Variant summary

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

The NM_006293.4(TYRO3):​c.1289T>C​(p.Val430Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TYRO3 NM_006293.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85

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.1289T>C	p.Val430Ala	missense_variant	10/19	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2	c.1154T>C	p.Val385Ala	missense_variant	10/19		NP_001317193.1
TYRO3	XM_017022543.3	c.1289T>C	p.Val430Ala	missense_variant	10/19		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8	c.1289T>C	p.Val430Ala	missense_variant	10/19	1	NM_006293.4	ENSP00000263798	A2
TYRO3	ENST00000559066.5	c.1154T>C	p.Val385Ala	missense_variant	10/19	5		ENSP00000454050	P4
TYRO3	ENST00000559815.1	c.343T>C	p.Tyr115His	missense_variant, NMD_transcript_variant	3/4	5		ENSP00000453835

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.1289T>C (p.V430A) alteration is located in exon 10 (coding exon 10) of the TYRO3 gene. This alteration results from a T to C substitution at nucleotide position 1289, causing the valine (V) at amino acid position 430 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	-0.016	T
MutationAssessor	Benign	1.9	.;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.48
Sift	Benign	0.15	T;T
Sift4G	Benign	0.56	T;T
Polyphen		1.0	.;D
Vest4		0.69
MutPred		0.43		.;Gain of glycosylation at S425 (P = 0.0734);
MVP		0.74
MPC		1.3
ClinPred		0.73	D
GERP RS		5.1
Varity_R		0.13
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-41862261;