NM_003265.3:c.-7C>T

Variant names:

• chr4-186076613-C-T
• rs3775296
• NM_003265.3:c.-7C>T

Variant summary

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

The NM_003265.3(TLR3):​c.-7C>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLR3 NM_003265.3 splice_region
• Scores: Splicing: ADA: 0.0005009
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 93 publications found

Genes affected

TLR3 (HGNC:11849): (toll like receptor 3) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of type I interferons. It thus plays a role in host defense against multiple viruses. [provided by RefSeq, Jul 2021]

TLR3 Gene-Disease associations (from GenCC):

• immunodeficiency 83, susceptibility to viral infections

  Inheritance: AR, AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

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=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003265.3. 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
	TLR3	NM_003265.3	MANE Select	c.-7C>T		splice_region	Exon 2 of 5	NP_003256.1	O15455-1
	TLR3	NM_003265.3	MANE Select	c.-7C>T		5_prime_UTR	Exon 2 of 5	NP_003256.1	O15455-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR3	ENST00000296795.8	TSL:1 MANE Select	c.-7C>T		splice_region	Exon 2 of 5	ENSP00000296795.3	O15455-1
	TLR3	ENST00000296795.8	TSL:1 MANE Select	c.-7C>T		5_prime_UTR	Exon 2 of 5	ENSP00000296795.3	O15455-1
	TLR3	ENST00000513189.1	TSL:1	n.-7C>T		splice_region non_coding_transcript_exon	Exon 2 of 5	ENSP00000423386.1	D6RA51

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.2
DANN	Benign	0.51
PhyloP100		-0.23

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00050
dbscSNV1_RF	Benign	0.052
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: rs3775296; hg19: chr4-186997767;