rs11466653

Positions:

• chr4-38774614-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030956.4(TLR10):​c.977T>C​(p.Met326Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0412 in 1,588,362 control chromosomes in the GnomAD database, including 2,771 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.044 (305 hom., cov: 33)
  • Exomes 𝑓: 0.041 (2466 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017455816).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR10	NM_030956.4	c.977T>C	p.Met326Thr	missense_variant	4/4	ENST00000308973.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR10	ENST00000308973.9	c.977T>C	p.Met326Thr	missense_variant	4/4	5	NM_030956.4	P1

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6760 AN: 152190 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.0937

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0670

GnomAD3 exomes AF: 0.0642 AC: 14567 AN: 226738 Hom.: 782 AF XY: 0.0665 AC XY: 8138 AN XY: 122368

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.0739

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.149

Gnomad FIN exome AF: 0.0204

Gnomad NFE exome AF: 0.0321

Gnomad OTH exome AF: 0.0650

GnomAD4 exome AF: 0.0409 AC: 58733 AN: 1436054 Hom.: 2466 Cov.: 36 AF XY: 0.0444 AC XY: 31637 AN XY: 713088

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.0789

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.0230

Gnomad4 NFE exome AF: 0.0264

Gnomad4 OTH exome AF: 0.0533

GnomAD4 genome AF: 0.0445 AC: 6772 AN: 152308 Hom.: 305 Cov.: 33 AF XY: 0.0471 AC XY: 3507 AN XY: 74476

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.0940

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0178

Gnomad4 NFE AF: 0.0293

Gnomad4 OTH AF: 0.0663

Alfa AF: 0.0400 Hom.: 301

Bravo AF: 0.0486

TwinsUK AF: 0.0235 AC: 87

ALSPAC AF: 0.0291 AC: 112

ESP6500AA AF: 0.0266 AC: 117

ESP6500EA AF: 0.0278 AC: 239

ExAC AF: 0.0663 AC: 8049

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T;T;T;T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.95	D
MetaRNN	Benign	0.0017	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.9	M;M;M;M;M;M
MutationTaster	Benign	0.017	P;P;P;P
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.6	D;.;D;.;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0050	D;.;D;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.87	P;P;P;P;P;P
Vest4		0.30
MPC		0.37
ClinPred		0.030	T
GERP RS		5.1
Varity_R		0.63
gMVP		0.42

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: rs11466653; hg19: chr4-38776235; COSMIC: COSV58302470; COSMIC: COSV58302470;