rs16971872

Variant names:

• chr15-41567272-T-C
• rs16971872
• NM_006293.4:c.784-88T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006293.4(TYRO3):​c.784-88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,164,046 control chromosomes in the GnomAD database, including 11,999 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 0.19 (3837 hom., cov: 32)
  • Exomes 𝑓: 0.12 (8162 hom.)
• Consequence: TYRO3 NM_006293.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRO3	NM_006293.4	c.784-88T>C		intron_variant	Intron 6 of 18	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2	c.649-88T>C		intron_variant	Intron 6 of 18		NP_001317193.1
TYRO3	XM_017022543.3	c.784-88T>C		intron_variant	Intron 6 of 18		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8	c.784-88T>C		intron_variant	Intron 6 of 18	1	NM_006293.4	ENSP00000263798.3
TYRO3	ENST00000559066.5	c.649-88T>C		intron_variant	Intron 6 of 18	5		ENSP00000454050.1
TYRO3	ENST00000560227.1	n.359-88T>C		intron_variant	Intron 1 of 2	5
TYRO3	ENST00000559815.1	n.-109T>C		upstream_gene_variant		5		ENSP00000453835.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28400 AN: 151918 Hom.: 3831 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.00751

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.118 AC: 119036 AN: 1012010 Hom.: 8162 AF XY: 0.117 AC XY: 57830 AN XY: 494068

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0726

Gnomad4 EAS exome AF: 0.00679

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.187 AC: 28439 AN: 152036 Hom.: 3837 Cov.: 32 AF XY: 0.184 AC XY: 13647 AN XY: 74324

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0715

Gnomad4 EAS AF: 0.00753

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.157

Alfa AF: 0.171 Hom.: 844

Bravo AF: 0.195

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.6
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs16971872; hg19: chr15-41859470; COSMIC: COSV55488208; COSMIC: COSV55488208;