15-41564882-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006293.4(TYRO3):​c.668-144A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 486,086 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TYRO3 NM_006293.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRO3	NM_006293.4	c.668-144A>C		intron_variant	Intron 5 of 18	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2	c.533-144A>C		intron_variant	Intron 5 of 18		NP_001317193.1
TYRO3	XM_017022543.3	c.668-144A>C		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>C		intron_variant	Intron 5 of 18	1	NM_006293.4	ENSP00000263798.3
TYRO3	ENST00000560227.1	n.99A>C		non_coding_transcript_exon_variant	Exon 1 of 3	5
TYRO3	ENST00000559066.5	c.533-144A>C		intron_variant	Intron 5 of 18	5		ENSP00000454050.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 1 AN: 486086 Hom.: 0 Cov.: 4 AF XY: 0.00000388 AC XY: 1 AN XY: 257600

African (AFR) AF: 0.00 AC: 0 AN: 14488

American (AMR) AF: 0.00 AC: 0 AN: 30544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15876

East Asian (EAS) AF: 0.00 AC: 0 AN: 30766

South Asian (SAS) AF: 0.0000192 AC: 1 AN: 52214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2110

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 281052

Other (OTH) AF: 0.00 AC: 0 AN: 27486

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.46
PhyloP100		-0.46

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;