15-41570104-G-A

Position:

• chr15-41570104-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006293.4(TYRO3):​c.1330G>A​(p.Ala444Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 8.57

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29103553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRO3	NM_006293.4	c.1330G>A	p.Ala444Thr	missense_variant	10/19	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2	c.1195G>A	p.Ala399Thr	missense_variant	10/19		NP_001317193.1
TYRO3	XM_017022543.3	c.1330G>A	p.Ala444Thr	missense_variant	10/19		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8	c.1330G>A	p.Ala444Thr	missense_variant	10/19	1	NM_006293.4	ENSP00000263798.3
TYRO3	ENST00000559066.5	c.1195G>A	p.Ala399Thr	missense_variant	10/19	5		ENSP00000454050.1
TYRO3	ENST00000559815.1	n.*18G>A		non_coding_transcript_exon_variant	3/4	5		ENSP00000453835.1
TYRO3	ENST00000559815.1	n.*18G>A		3_prime_UTR_variant	3/4	5		ENSP00000453835.1

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

Jan 09, 2024

The c.1330G>A (p.A444T) alteration is located in exon 10 (coding exon 10) of the TYRO3 gene. This alteration results from a G to A substitution at nucleotide position 1330, causing the alanine (A) at amino acid position 444 to be replaced by a threonine (T). 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	Benign	0.097
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.017	T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.90	.;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.25	N;N
REVEL	Benign	0.25
Sift	Benign	0.067	T;T
Sift4G	Benign	0.072	T;T
Polyphen		0.87	.;P
Vest4		0.39
MutPred		0.44		.;Loss of MoRF binding (P = 0.136);
MVP		0.34
MPC		0.74
ClinPred		0.81	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.095
gMVP		0.48

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: chr15-41862302;