Variant 4-38775104-C-A 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.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. 13/20 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 0.048 ( 328 hom., cov: 32)

Exomes 𝑓: 0.043 ( 2746 hom. )

Consequence

TLR10
NM_030956.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.139

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=0.0013934672).

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/exons	MANE	UniProt
TLR10	NM_030956.4 linkuse as main transcript	c.487G>T	p.Ala163Ser	missense_variant	4/4	ENST00000308973.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR10	ENST00000308973.9 linkuse as main transcript	c.487G>T	p.Ala163Ser	missense_variant	4/4	5	NM_030956.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0484

AC:

7359

AN:

152090

Hom.:

321

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0710

AC:

17718

AN:

249552

Hom.:

1024

AF XY:

0.0730

AC XY:

9864

AN XY:

135108

show subpopulations

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 SAS exome

AF:

0.155

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.:

AF XY:

0.0463

AC XY:

33650

AN XY:

726674

show subpopulations

Gnomad4 AFR exome

AF:

0.0394

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.0807

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.0231

Gnomad4 NFE exome

AF:

0.0267

Gnomad4 OTH exome

AF:

0.0554

GnomAD4 genome

AF:

0.0484

AC:

7372

AN:

152210

Hom.:

328

Cov.:

AF XY:

0.0511

AC XY:

3805

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0401

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.0839

Gnomad4 EAS

AF:

0.0940

Gnomad4 SAS

AF:

0.152

Gnomad4 FIN

AF:

0.0179

Gnomad4 NFE

AF:

0.0293

Gnomad4 OTH

AF:

0.0687

Alfa

AF:

0.0396

Hom.:

223

Bravo

AF:

0.0531

TwinsUK

AF:

0.0237

AC:

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

BayesDel_noAF

Benign

-0.68

CADD

Benign

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

LIST_S2

Benign

0.58

.;.;.;T;.;.

MetaRNN

Benign

0.0014

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;L;L;L;L

MutationTaster

Benign

0.14

P;P;P;P

PrimateAI

Benign

0.26

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

GERP RS

4.4

Varity_R

0.11

gMVP

0.097

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