rs2052127816

Variant names:

• chr15-41559285-C-G
• NM_006293.4:c.28C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-41559285-C-G
• chr15-41559285-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006293.4(TYRO3):​c.28C>G​(p.Pro10Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P10S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 35)
• Consequence: TYRO3 NM_006293.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17329028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRO3	NM_006293.4	c.28C>G	p.Pro10Ala	missense_variant	Exon 1 of 19	ENST00000263798.8	NP_006284.2
TYRO3	XM_017022543.3	c.28C>G	p.Pro10Ala	missense_variant	Exon 1 of 19		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8	c.28C>G	p.Pro10Ala	missense_variant	Exon 1 of 19	1	NM_006293.4	ENSP00000263798.3
TYRO3	ENST00000559066.5	c.-12+813C>G		intron_variant	Intron 1 of 18	5		ENSP00000454050.1
TYRO3	ENST00000560992.1	n.59C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.81
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.15
Sift	Benign	0.054	T
Sift4G	Benign	0.10	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.10		Loss of glycosylation at P10 (P = 0.0238);
MVP		0.20
MPC		0.38
ClinPred		0.060	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.062
gMVP		0.34

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: chr15-41851483;