Variant 4-38774486-T-G 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.1105A>C(p.Ile369Leu) 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 1,596,826 control chromosomes in the GnomAD database, including 109,548 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 0.42 ( 13913 hom., cov: 32)

Exomes 𝑓: 0.35 ( 95635 hom. )

Consequence

TLR10
NM_030956.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.577

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=7.11327E-5).

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.1105A>C	p.Ile369Leu	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.1105A>C	p.Ile369Leu	missense_variant	4/4	5	NM_030956.4	ENSP00000308925.4		Q9BXR5

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63424

AN:

151922

Hom.:

13875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.516

Gnomad AMI

AF:

0.391

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.502

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.590

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.473

GnomAD3 exomes

AF:

0.415

AC:

97281

AN:

234678

Hom.:

21227

AF XY:

0.423

AC XY:

53597

AN XY:

126784

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.343

Gnomad ASJ exome

AF:

0.495

Gnomad EAS exome

AF:

0.533

Gnomad SAS exome

AF:

0.562

Gnomad FIN exome

AF:

0.349

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.419

GnomAD4 exome

AF:

0.351

AC:

507525

AN:

1444786

Hom.:

95635

Cov.:

AF XY:

0.360

AC XY:

258378

AN XY:

717960

show subpopulations

Gnomad4 AFR exome

AF:

0.527

Gnomad4 AMR exome

AF:

0.351

Gnomad4 ASJ exome

AF:

0.496

Gnomad4 EAS exome

AF:

0.573

Gnomad4 SAS exome

AF:

0.560

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.317

Gnomad4 OTH exome

AF:

0.379

GnomAD4 genome

AF:

0.418

AC:

63499

AN:

152040

Hom.:

13913

Cov.:

AF XY:

0.418

AC XY:

31079

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.516

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.502

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:

0.380

Hom.:

15722

Bravo

AF:

0.423

TwinsUK

AF:

0.316

AC:

1171

ALSPAC

AF:

0.335

AC:

1293

ESP6500AA

AF:

0.507

AC:

2232

ESP6500EA

AF:

0.343

AC:

2951

ExAC

AF:

0.428

AC:

51975

Asia WGS

AF:

0.514

AC:

1789

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.7

DANN

Benign

0.86

DEOGEN2

Benign

0.017

T;T;T;T;T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.21

.;.;.;T;.;.

MetaRNN

Benign

0.000071

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.13

N;.;N;.;N;N

REVEL

Benign

0.035

Sift

Benign

0.33

T;.;T;.;T;T

Sift4G

Benign

0.31

T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;B;B

Vest4

0.051

MPC

0.053

ClinPred

0.0022

GERP RS

1.2

Varity_R

0.066

gMVP

0.51

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