NM_138636.5:c.1312C>A

Variant names:

• chrX-12920352-C-A
• rs5744081
• NM_138636.5:c.1312C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138636.5(TLR8):​c.1312C>A​(p.Arg438Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,209,090 control chromosomes in the GnomAD database, including 1,427 homozygotes. There are 4,331 hemizygotes in GnomAD. 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 0.072 (728 hom., 2187 hem., cov: 23)
  • Exomes 𝑓: 0.0076 (699 hom. 2144 hem.)
• Consequence: TLR8 NM_138636.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659
• Publications: 6 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.659 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138636.5. 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
	TLR8	NM_138636.5	MANE Select	c.1312C>A	p.Arg438Arg	synonymous	Exon 2 of 2	NP_619542.1	Q9NR97-1
	TLR8	NM_016610.4		c.1366C>A	p.Arg456Arg	synonymous	Exon 3 of 3	NP_057694.2
	TLR8-AS1	NR_030727.1		n.241-12019G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	ENST00000218032.7	TSL:1 MANE Select	c.1312C>A	p.Arg438Arg	synonymous	Exon 2 of 2	ENSP00000218032.7	Q9NR97-1
	TLR8	ENST00000311912.5	TSL:1	c.1366C>A	p.Arg456Arg	synonymous	Exon 3 of 3	ENSP00000312082.5	Q9NR97-2

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 8080 AN: 112068 Hom.: 727 Cov.: 23

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000729

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000619

Gnomad OTH AF: 0.0558

GnomAD2 exomes AF: 0.0203 AC: 3676 AN: 181459 AF XY: 0.0131

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.0103

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000406

Gnomad OTH exome AF: 0.00693

GnomAD4 exome AF: 0.00763 AC: 8373 AN: 1096970 Hom.: 699 Cov.: 34 AF XY: 0.00592 AC XY: 2144 AN XY: 362438

African (AFR) AF: 0.259 AC: 6814 AN: 26335

American (AMR) AF: 0.0135 AC: 472 AN: 35073

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19365

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30181

South Asian (SAS) AF: 0.000464 AC: 25 AN: 53877

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40418

Middle Eastern (MID) AF: 0.00727 AC: 30 AN: 4129

European-Non Finnish (NFE) AF: 0.000303 AC: 255 AN: 841547

Other (OTH) AF: 0.0168 AC: 775 AN: 46045

GnomAD4 genome AF: 0.0722 AC: 8100 AN: 112120 Hom.: 728 Cov.: 23 AF XY: 0.0637 AC XY: 2187 AN XY: 34334

African (AFR) AF: 0.249 AC: 7664 AN: 30736

American (AMR) AF: 0.0295 AC: 313 AN: 10621

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3609

South Asian (SAS) AF: 0.000732 AC: 2 AN: 2733

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6056

Middle Eastern (MID) AF: 0.0140 AC: 3 AN: 215

European-Non Finnish (NFE) AF: 0.000619 AC: 33 AN: 53269

Other (OTH) AF: 0.0551 AC: 85 AN: 1543

Alfa AF: 0.0290 Hom.: 2358

Bravo AF: 0.0828

EpiCase AF: 0.000437

EpiControl AF: 0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.38
PhyloP100		-0.66
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: rs5744081; hg19: chrX-12938471;