rs11466649

Variant names:

• chr4-38775104-C-A
• rs11466649
• NM_030956.4:c.487G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030956.4(TLR10):​c.487G>T​(p.Ala163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 1,612,884 control chromosomes in the GnomAD database, including 3,074 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.048 (328 hom., cov: 32)
  • Exomes 𝑓: 0.043 (2746 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013934672).
• 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 rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.487G>T	p.Ala163Ser	missense_variant	Exon 4 of 4	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.487G>T	p.Ala163Ser	missense_variant	Exon 4 of 4	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7359 AN: 152090 Hom.: 321 Cov.: 32

Gnomad AFR AF: 0.0402

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.0936

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0694

GnomAD2 exomes AF: 0.0710 AC: 17718 AN: 249552 AF XY: 0.0730

Gnomad AFR exome AF: 0.0394

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.0772

Gnomad EAS exome AF: 0.100

Gnomad FIN exome AF: 0.0205

Gnomad NFE exome AF: 0.0330

Gnomad OTH exome AF: 0.0704

GnomAD4 exome AF: 0.0428 AC: 62492 AN: 1460674 Hom.: 2746 Cov.: 35 AF XY: 0.0463 AC XY: 33650 AN XY: 726674

African (AFR) AF: 0.0394 AC: 1320 AN: 33472

American (AMR) AF: 0.147 AC: 6585 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 2107 AN: 26124

East Asian (EAS) AF: 0.101 AC: 4019 AN: 39694

South Asian (SAS) AF: 0.158 AC: 13611 AN: 86166

European-Finnish (FIN) AF: 0.0231 AC: 1213 AN: 52440

Middle Eastern (MID) AF: 0.113 AC: 649 AN: 5768

European-Non Finnish (NFE) AF: 0.0267 AC: 29643 AN: 1111958

Other (OTH) AF: 0.0554 AC: 3345 AN: 60386

GnomAD4 genome AF: 0.0484 AC: 7372 AN: 152210 Hom.: 328 Cov.: 32 AF XY: 0.0511 AC XY: 3805 AN XY: 74420

African (AFR) AF: 0.0401 AC: 1664 AN: 41520

American (AMR) AF: 0.121 AC: 1849 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.0940 AC: 487 AN: 5182

South Asian (SAS) AF: 0.152 AC: 735 AN: 4832

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10598

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0293 AC: 1993 AN: 68004

Other (OTH) AF: 0.0687 AC: 145 AN: 2110

Alfa AF: 0.0400 Hom.: 553

Bravo AF: 0.0531

TwinsUK AF: 0.0237 AC: 88

ALSPAC AF: 0.0288 AC: 111

ESP6500AA AF: 0.0388 AC: 171

ESP6500EA AF: 0.0274 AC: 236

ExAC AF: 0.0684 AC: 8300

Asia WGS AF: 0.113 AC: 393 AN: 3478

EpiCase AF: 0.0364

EpiControl AF: 0.0360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.029	T;T;T;T;T;T
Eigen	Benign	-0.078
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.58	.;.;.;T;.;.
MetaRNN	Benign	0.0014	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;L;L;L
PhyloP100		0.14
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.6	N;.;N;.;N;N
REVEL	Benign	0.060
Sift	Benign	0.061	T;.;T;.;T;T
Sift4G	Benign	0.11	T;T;T;T;T;T
Polyphen		0.17	B;B;B;B;B;B
Vest4		0.038
MPC		0.081
ClinPred		0.0080	T
GERP RS		4.4
Varity_R		0.11
gMVP		0.097
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: rs11466649; hg19: chr4-38776725; COSMIC: COSV58300733; COSMIC: COSV58300733;