Genetic Variant TYRO3:c.*1018A>G (chr15-41579294-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006293.4(TYRO3):c.*1018A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 151,946 control chromosomes in the GnomAD database, including 58 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 0.028 ( 58 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TYRO3
NM_006293.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.73

Publications

9 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=-0.55).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0279 (4238/151946) while in subpopulation NFE AF = 0.0398 (2704/67990). AF 95% confidence interval is 0.0385. There are 58 homozygotes in GnomAd4. There are 1917 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 58 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRO3	NM_006293.4 link	c.*1018A>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000263798.8	NP_006284.2	Q06418
TYRO3	NM_001330264.2 link	c.*1018A>G		3_prime_UTR_variant	Exon 19 of 19		NP_001317193.1	Q06418H0YNK6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8 link	c.*1018A>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_006293.4	ENSP00000263798.3		Q06418
TYRO3	ENST00000568490.1 link	n.1960A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4239

AN:

151842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00782

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0880

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0181

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0398

Gnomad OTH

AF:

0.0422

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0279

AC:

4238

AN:

151946

Hom.:

Cov.:

AF XY:

0.0258

AC XY:

1917

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.00780

AC:

323

AN:

41426

American (AMR)

AF:

0.0343

AC:

523

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0880

AC:

305

AN:

3466

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.0110

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0181

AC:

190

AN:

10520

Middle Eastern (MID)

AF:

0.0788

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0398

AC:

2704

AN:

67990

Other (OTH)

AF:

0.0417

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

182

364

545

727

909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0335

Hom.:

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

2.7

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over