Variant rs11096957 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.721A>C(p.Asn241His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,605,706 control chromosomes in the GnomAD database, including 110,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.42 ( 13903 hom., cov: 33)

Exomes 𝑓: 0.35 ( 96826 hom. )

Consequence

TLR10
NM_030956.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.31

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=7.4726343E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 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.721A>C	p.Asn241His	missense_variant	4/4	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9 linkuse as main transcript	c.721A>C	p.Asn241His	missense_variant	4/4	5	NM_030956.4	ENSP00000308925	P1

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63429

AN:

151954

Hom.:

13865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.516

Gnomad AMI

AF:

0.391

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.473

GnomAD3 exomes

AF:

0.416

AC:

101773

AN:

244642

Hom.:

22385

AF XY:

0.425

AC XY:

56222

AN XY:

132304

show subpopulations

Gnomad AFR exome

AF:

0.518

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.494

Gnomad EAS exome

AF:

0.533

Gnomad SAS exome

AF:

0.565

Gnomad FIN exome

AF:

0.349

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.352

AC:

511998

AN:

1453632

Hom.:

96826

Cov.:

AF XY:

0.361

AC XY:

260883

AN XY:

722578

show subpopulations

Gnomad4 AFR exome

AF:

0.528

Gnomad4 AMR exome

AF:

0.354

Gnomad4 ASJ exome

AF:

0.497

Gnomad4 EAS exome

AF:

0.573

Gnomad4 SAS exome

AF:

0.562

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.317

Gnomad4 OTH exome

AF:

0.380

GnomAD4 genome

AF:

0.418

AC:

63504

AN:

152074

Hom.:

13903

Cov.:

AF XY:

0.418

AC XY:

31082

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.516

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.501

Gnomad4 EAS

AF:

0.534

Gnomad4 SAS

AF:

0.547

Gnomad4 FIN

AF:

0.345

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.473

Alfa

AF:

0.383

Hom.:

25363

Bravo

AF:

0.423

TwinsUK

AF:

0.316

AC:

1170

ALSPAC

AF:

0.336

AC:

1294

ESP6500AA

AF:

0.506

AC:

2231

ESP6500EA

AF:

0.343

AC:

2951

ExAC

AF:

0.428

AC:

51977

Asia WGS

AF:

0.514

AC:

1791

AN:

3478

EpiCase

AF:

0.365

EpiControl

AF:

0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T;T;T;T;T

Eigen

Benign

0.017

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.52

.;.;.;T;.;.

MetaRNN

Benign

0.00075

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.6

M;M;M;M;M;M

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.4

N;.;N;.;N;N

REVEL

Benign

0.29

Sift

Uncertain

0.0070

D;.;D;.;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D

Polyphen

0.86

P;P;P;P;P;P

Vest4

0.15

MPC

0.25

ClinPred

0.052

GERP RS

4.9

Varity_R

0.17

gMVP

0.25

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