15-41564882-A-G

Variant names:

• chr15-41564882-A-G
• rs2277537
• NM_006293.4:c.668-144A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 8 publications found

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRO3	NM_006293.4	c.668-144A>G		intron_variant	Intron 5 of 18	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2	c.533-144A>G		intron_variant	Intron 5 of 18		NP_001317193.1
TYRO3	XM_017022543.3	c.668-144A>G		intron_variant	Intron 5 of 18		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8	c.668-144A>G		intron_variant	Intron 5 of 18	1	NM_006293.4	ENSP00000263798.3
TYRO3	ENST00000560227.1	n.99A>G		non_coding_transcript_exon_variant	Exon 1 of 3	5
TYRO3	ENST00000559066.5	c.533-144A>G		intron_variant	Intron 5 of 18	5		ENSP00000454050.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73449 AN: 151820 Hom.: 18932 Cov.: 32

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.: 4 AF XY: 0.448 AC XY: 115232 AN XY: 257174

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

GnomAD4 genome AF: 0.484 AC: 73532 AN: 151938 Hom.: 18959 Cov.: 32 AF XY: 0.484 AC XY: 35918 AN XY: 74254

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.89
DANN	Benign	0.46
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2277537; hg19: chr15-41857080;