rs11466658

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_030956.4(TLR10):c.1573C>T(p.Arg525Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,606,620 control chromosomes in the GnomAD database, including 706 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R525Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.025 ( 63 hom., cov: 32)

Exomes 𝑓: 0.027 ( 643 hom. )

Consequence

TLR10
NM_030956.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.257

Publications

24 publications found

Variant links:

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]

TLR10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0037816763).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0253 (3852/152228) while in subpopulation SAS AF = 0.0437 (211/4826). AF 95% confidence interval is 0.0389. There are 63 homozygotes in GnomAd4. There are 1849 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 63 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030956.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLR10	NM_030956.4	MANE Select	c.1573C>T	p.Arg525Trp	missense	Exon 4 of 4	NP_112218.2	Q9BXR5
TLR10	NM_001017388.3		c.1573C>T	p.Arg525Trp	missense	Exon 2 of 2	NP_001017388.1	Q9BXR5
TLR10	NM_001195106.2		c.1573C>T	p.Arg525Trp	missense	Exon 3 of 3	NP_001182035.1	Q9BXR5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLR10	ENST00000308973.9	TSL:5 MANE Select	c.1573C>T	p.Arg525Trp	missense	Exon 4 of 4	ENSP00000308925.4	Q9BXR5
TLR10	ENST00000361424.6	TSL:1	c.1573C>T	p.Arg525Trp	missense	Exon 2 of 2	ENSP00000354459.2	Q9BXR5
TLR10	ENST00000506111.1	TSL:1	c.1573C>T	p.Arg525Trp	missense	Exon 2 of 2	ENSP00000421483.1	Q9BXR5

Frequencies

GnomAD3 genomes

AF:

0.0253

AC:

3842

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0247

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.0113

Gnomad SAS

AF:

0.0437

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0275

Gnomad OTH

AF:

0.0360

GnomAD2 exomes

AF:

0.0271

AC:

6663

AN:

246100

AF XY:

0.0287

show subpopulations

Gnomad AFR exome

AF:

0.0244

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.0355

Gnomad EAS exome

AF:

0.00895

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.0320

Gnomad OTH exome

AF:

0.0247

GnomAD4 exome

AF:

0.0270

AC:

39296

AN:

1454392

Hom.:

643

Cov.:

AF XY:

0.0276

AC XY:

19933

AN XY:

722780

show subpopulations

African (AFR)

AF:

0.0239

AC:

793

AN:

33178

American (AMR)

AF:

0.0158

AC:

689

AN:

43556

Ashkenazi Jewish (ASJ)

AF:

0.0336

AC:

870

AN:

25858

East Asian (EAS)

AF:

0.00384

AC:

152

AN:

39568

South Asian (SAS)

AF:

0.0392

AC:

3335

AN:

85144

European-Finnish (FIN)

AF:

0.0161

AC:

857

AN:

53280

Middle Eastern (MID)

AF:

0.0330

AC:

189

AN:

5732

European-Non Finnish (NFE)

AF:

0.0278

AC:

30818

AN:

1108024

Other (OTH)

AF:

0.0265

AC:

1593

AN:

60052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2187

4375

6562

8750

10937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1114

2228

3342

4456

5570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0253

AC:

3852

AN:

152228

Hom.:

Cov.:

AF XY:

0.0248

AC XY:

1849

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0234

AC:

973

AN:

41526

American (AMR)

AF:

0.0247

AC:

377

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

104

AN:

3472

East Asian (EAS)

AF:

0.0114

AC:

AN:

5190

South Asian (SAS)

AF:

0.0437

AC:

211

AN:

4826

European-Finnish (FIN)

AF:

0.0142

AC:

150

AN:

10598

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0275

AC:

1872

AN:

68024

Other (OTH)

AF:

0.0399

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

195

390

585

780

975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0274

Hom.:

198

Bravo

AF:

0.0255

TwinsUK

AF:

0.0280

AC:

104

ALSPAC

AF:

0.0280

AC:

108

ESP6500AA

AF:

0.0243

AC:

107

ESP6500EA

AF:

0.0313

AC:

269

ExAC

AF:

0.0291

AC:

3535

Asia WGS

AF:

0.0450

AC:

159

AN:

3478

EpiCase

AF:

0.0277

EpiControl

AF:

0.0289

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.27

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

-0.26

PrimateAI

Benign

0.18

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.034

Sift

Uncertain

0.027

Sift4G

Uncertain

0.0060

Polyphen

0.0040

Vest4

0.077

MPC

0.055

ClinPred

0.0080

GERP RS

-1.7

Varity_R

0.099

gMVP

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over