chrX-12906707-A-T

Variant names:

• chrX-12906707-A-T
• rs3764880
• ENST00000311912.5:c.-83A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000311912.5(TLR8):​c.-83A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TLR8 ENST00000311912.5 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.0001027
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 157 publications found

Genes affected

TLR8 (HGNC:15632): (toll like receptor 8) 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 gene is predominantly expressed in lung and peripheral blood leukocytes, and lies in close proximity to another family member, TLR7, on chromosome X. [provided by RefSeq, Jul 2008]

TLR8-AS1 (HGNC:40720): (TLR8 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000311912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	NM_138636.5	MANE Select	c.1A>T	p.Met1?	initiator_codon splice_region	Exon 1 of 2	NP_619542.1
	TLR8	NM_016610.4		c.-83A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_057694.2
	TLR8	NM_016610.4		c.-83A>T		splice_region	Exon 1 of 3	NP_057694.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	ENST00000311912.5	TSL:1	c.-83A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000312082.5
	TLR8	ENST00000218032.7	TSL:1 MANE Select	c.1A>T	p.Met1?	initiator_codon splice_region	Exon 1 of 2	ENSP00000218032.7
	TLR8	ENST00000311912.5	TSL:1	c.-83A>T		splice_region	Exon 1 of 3	ENSP00000312082.5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 998025 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 314485

African (AFR) AF: 0.00 AC: 0 AN: 22328

American (AMR) AF: 0.00 AC: 0 AN: 19552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15572

East Asian (EAS) AF: 0.00 AC: 0 AN: 25012

South Asian (SAS) AF: 0.00 AC: 0 AN: 35093

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37653

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3755

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 797672

Other (OTH) AF: 0.00 AC: 0 AN: 41388

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.029
DANN	Benign	0.43
DEOGEN2	Benign	0.081	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0042	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
PhyloP100		-0.62
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.97		Loss of disorder (P = 0.1126)
MVP		0.068
ClinPred		0.096	T
GERP RS		-3.6
PromoterAI		-0.13	Neutral
Varity_R		0.65
Mutation Taster		=169/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.056
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: rs3764880; hg19: chrX-12924826;