rs11096956

Positions:

• chr4-38774559-C-A
• chr4-38774559-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_030956.4(TLR10):​c.1032G>T​(p.Pro344=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,591,732 control chromosomes in the GnomAD database, including 42,029 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 0.23 (4585 hom., cov: 33)
  • Exomes 𝑓: 0.21 (37444 hom.)
• Consequence: TLR10 NM_030956.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

TLR10 (HGNC:15634): (toll like receptor 10) 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 most highly expressed in lymphoid tissues such as spleen, lymph node, thymus, and tonsil. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR10	NM_030956.4	c.1032G>T	p.Pro344=	synonymous_variant	4/4	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.1032G>T	p.Pro344=	synonymous_variant	4/4	5	NM_030956.4	ENSP00000308925	P1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35430 AN: 151990 Hom.: 4580 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.290

GnomAD3 exomes AF: 0.251 AC: 58047 AN: 231240 Hom.: 8289 AF XY: 0.256 AC XY: 32022 AN XY: 124958

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.261

Gnomad ASJ exome AF: 0.365

Gnomad EAS exome AF: 0.425

Gnomad SAS exome AF: 0.341

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.212 AC: 305695 AN: 1439624 Hom.: 37444 Cov.: 36 AF XY: 0.218 AC XY: 155565 AN XY: 714946

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.233 AC: 35446 AN: 152108 Hom.: 4585 Cov.: 33 AF XY: 0.231 AC XY: 17178 AN XY: 74356

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.0964

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.287

Alfa AF: 0.231 Hom.: 7545

Bravo AF: 0.250

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.3
DANN	Benign	0.49

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: rs11096956; hg19: chr4-38776180;