Genetic Variant TYRO3:c.668-144A>G (chr15-41564882-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006293.4(TYRO3):c.668-144A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 637,230 control chromosomes in the GnomAD database, including 71,051 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 18959 hom., cov: 32)

Exomes 𝑓: 0.45 ( 52092 hom. )

Consequence

TYRO3
NM_006293.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.457

Publications

8 publications found

Variant links:

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]

TYRO3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

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.668-144A>G		intron	N/A	NP_006284.2
	TYRO3	NM_001330264.2		c.533-144A>G		intron	N/A	NP_001317193.1	H0YNK6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TYRO3	ENST00000263798.8	TSL:1 MANE Select	c.668-144A>G	intron	N/A	ENSP00000263798.3	Q06418
TYRO3	ENST00000869540.1		c.668-144A>G	intron	N/A	ENSP00000539599.1
TYRO3	ENST00000869541.1		c.668-144A>G	intron	N/A	ENSP00000539600.1

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73449

AN:

151820

Hom.:

18932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.352

Gnomad EAS

AF:

0.824

Gnomad SAS

AF:

0.474

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.460

GnomAD4 exome

AF:

0.448

AC:

217608

AN:

485292

Hom.:

52092

Cov.:

AF XY:

0.448

AC XY:

115232

AN XY:

257174

show subpopulations

African (AFR)

AF:

0.630

AC:

9103

AN:

14452

American (AMR)

AF:

0.438

AC:

13365

AN:

30482

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

5647

AN:

15832

East Asian (EAS)

AF:

0.831

AC:

25564

AN:

30762

South Asian (SAS)

AF:

0.487

AC:

25383

AN:

52148

European-Finnish (FIN)

AF:

0.387

AC:

12203

AN:

31500

Middle Eastern (MID)

AF:

0.404

AC:

852

AN:

2108

European-Non Finnish (NFE)

AF:

0.405

AC:

113623

AN:

280568

Other (OTH)

AF:

0.433

AC:

11868

AN:

27440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

5126

10253

15379

20506

25632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

770

1540

2310

3080

3850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.484

AC:

73532

AN:

151938

Hom.:

18959

Cov.:

AF XY:

0.484

AC XY:

35918

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.632

AC:

26207

AN:

41454

American (AMR)

AF:

0.415

AC:

6337

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

1220

AN:

3462

East Asian (EAS)

AF:

0.824

AC:

4248

AN:

5158

South Asian (SAS)

AF:

0.475

AC:

2289

AN:

4816

European-Finnish (FIN)

AF:

0.385

AC:

4059

AN:

10556

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.407

AC:

27663

AN:

67918

Other (OTH)

AF:

0.460

AC:

969

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1862

3723

5585

7446

9308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.417

Hom.:

16170

Bravo

AF:

0.496

Asia WGS

AF:

0.626

AC:

2175

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.89

(source)

DANN

Benign

0.46

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over