Variant rs11466655 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030956.4(TLR10):c.1142G>A(p.Gly381Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,611,924 control chromosomes in the GnomAD database, including 1,328 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 159 hom., cov: 32)

Exomes 𝑓: 0.016 ( 1169 hom. )

Consequence

TLR10
NM_030956.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.544

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003190428).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR10	NM_030956.4 linkuse as main transcript	c.1142G>A	p.Gly381Asp	missense_variant	4/4	ENST00000308973.9	NP_112218.2	Q9BXR5A0A024R9W4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9 linkuse as main transcript	c.1142G>A	p.Gly381Asp	missense_variant	4/4	5	NM_030956.4	ENSP00000308925.4		Q9BXR5

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3383

AN:

152156

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.0627

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00605

Gnomad OTH

AF:

0.0272

GnomAD3 exomes

AF:

0.0323

AC:

8021

AN:

248502

Hom.:

555

AF XY:

0.0338

AC XY:

4534

AN XY:

134222

show subpopulations

Gnomad AFR exome

AF:

0.0273

Gnomad AMR exome

AF:

0.00675

Gnomad ASJ exome

AF:

0.0256

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.0622

Gnomad FIN exome

AF:

0.00325

Gnomad NFE exome

AF:

0.00837

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0161

AC:

23531

AN:

1459650

Hom.:

1169

Cov.:

AF XY:

0.0178

AC XY:

12912

AN XY:

725976

show subpopulations

Gnomad4 AFR exome

AF:

0.0291

Gnomad4 AMR exome

AF:

0.00730

Gnomad4 ASJ exome

AF:

0.0243

Gnomad4 EAS exome

AF:

0.186

Gnomad4 SAS exome

AF:

0.0640

Gnomad4 FIN exome

AF:

0.00369

Gnomad4 NFE exome

AF:

0.00593

Gnomad4 OTH exome

AF:

0.0284

GnomAD4 genome

AF:

0.0222

AC:

3387

AN:

152274

Hom.:

159

Cov.:

AF XY:

0.0239

AC XY:

1780

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0283

Gnomad4 AMR

AF:

0.0121

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.0632

Gnomad4 FIN

AF:

0.00236

Gnomad4 NFE

AF:

0.00606

Gnomad4 OTH

AF:

0.0274

Alfa

AF:

0.0155

Hom.:

202

Bravo

AF:

0.0227

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.0259

AC:

114

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.0328

AC:

3982

Asia WGS

AF:

0.117

AC:

405

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.090

DANN

Benign

0.56

DEOGEN2

Benign

0.045

T;T;T;T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.44

.;.;.;T;.;.

MetaRNN

Benign

0.0032

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;L;L;L;L;L

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.4

N;.;N;.;N;N

REVEL

Benign

0.0090

Sift

Benign

0.34

T;.;T;.;T;T

Sift4G

Benign

0.38

T;T;T;T;T;T

Polyphen

0.0010

B;B;B;B;B;B

Vest4

0.060

MPC

0.070

ClinPred

0.0039

GERP RS

-1.6

Varity_R

0.073

gMVP

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over