Genetic Variant TLR10:p.Ile775Val (chr4-38773268-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030956.4(TLR10):c.2323A>G(p.Ile775Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,611,796 control chromosomes in the GnomAD database, including 23,983 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.14 ( 1872 hom., cov: 32)

Exomes 𝑓: 0.16 ( 22111 hom. )

Consequence

TLR10
NM_030956.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.339

Publications

89 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.005084753).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4 link	c.2323A>G	p.Ile775Val	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 link	c.2323A>G	p.Ile775Val	missense_variant	Exon 4 of 4	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20588

AN:

152064

Hom.:

1872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.0781

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.188

GnomAD2 exomes

AF:

0.168

AC:

41690

AN:

248768

AF XY:

0.175

show subpopulations

Gnomad AFR exome

AF:

0.0265

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.0812

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.164

AC:

239772

AN:

1459614

Hom.:

22111

Cov.:

AF XY:

0.167

AC XY:

121121

AN XY:

726070

show subpopulations

African (AFR)

AF:

0.0285

AC:

950

AN:

33338

American (AMR)

AF:

0.120

AC:

5303

AN:

44126

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

6931

AN:

26026

East Asian (EAS)

AF:

0.346

AC:

13747

AN:

39692

South Asian (SAS)

AF:

0.189

AC:

16213

AN:

85694

European-Finnish (FIN)

AF:

0.0837

AC:

4467

AN:

53382

Middle Eastern (MID)

AF:

0.254

AC:

1465

AN:

5762

European-Non Finnish (NFE)

AF:

0.163

AC:

181166

AN:

1111312

Other (OTH)

AF:

0.158

AC:

9530

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

11009

22018

33028

44037

55046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6288

12576

18864

25152

31440

<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:

0.135

AC:

20580

AN:

152182

Hom.:

1872

Cov.:

AF XY:

0.132

AC XY:

9856

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0316

AC:

1312

AN:

41548

American (AMR)

AF:

0.168

AC:

2570

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

956

AN:

3470

East Asian (EAS)

AF:

0.276

AC:

1421

AN:

5154

South Asian (SAS)

AF:

0.177

AC:

851

AN:

4820

European-Finnish (FIN)

AF:

0.0781

AC:

828

AN:

10604

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11926

AN:

67978

Other (OTH)

AF:

0.185

AC:

391

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

849

1697

2546

3394

4243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<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:

0.177

Hom.:

8394

Bravo

AF:

0.141

TwinsUK

AF:

0.171

AC:

633

ALSPAC

AF:

0.188

AC:

726

ESP6500AA

AF:

0.0293

AC:

129

ESP6500EA

AF:

0.173

AC:

1492

ExAC

AF:

0.174

AC:

21106

Asia WGS

AF:

0.164

AC:

571

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.14

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.027

T;T;T;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.63

.;.;.;T;.;.

MetaRNN

Benign

0.0051

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.3

L;L;L;L;L;L

PhyloP100

-0.34

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.73

N;.;N;.;N;N

REVEL

Benign

0.043

Sift

Benign

0.23

T;.;T;.;T;T

Sift4G

Benign

0.22

T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;B;B

Vest4

0.029

MPC

0.047

ClinPred

0.00030

GERP RS

-5.3

Varity_R

0.12

gMVP

0.062

Mutation Taster

=95/5

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over