Genetic Variant NM_030956.4:c.1142G>A (chr4-38774449-C-T) – 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.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. 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 0.022 ( 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

Publications

26 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=0.003190428).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030956.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLR10	NM_030956.4	MANE Select	c.1142G>A	p.Gly381Asp	missense	Exon 4 of 4	NP_112218.2	Q9BXR5
TLR10	NM_001017388.3		c.1142G>A	p.Gly381Asp	missense	Exon 2 of 2	NP_001017388.1	Q9BXR5
TLR10	NM_001195106.2		c.1142G>A	p.Gly381Asp	missense	Exon 3 of 3	NP_001182035.1	Q9BXR5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLR10	ENST00000308973.9	TSL:5 MANE Select	c.1142G>A	p.Gly381Asp	missense	Exon 4 of 4	ENSP00000308925.4	Q9BXR5
TLR10	ENST00000361424.6	TSL:1	c.1142G>A	p.Gly381Asp	missense	Exon 2 of 2	ENSP00000354459.2	Q9BXR5
TLR10	ENST00000506111.1	TSL:1	c.1142G>A	p.Gly381Asp	missense	Exon 2 of 2	ENSP00000421483.1	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

GnomAD2 exomes

AF:

0.0323

AC:

8021

AN:

248502

AF XY:

0.0338

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 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

African (AFR)

AF:

0.0291

AC:

971

AN:

33382

American (AMR)

AF:

0.00730

AC:

323

AN:

44236

Ashkenazi Jewish (ASJ)

AF:

0.0243

AC:

633

AN:

26052

East Asian (EAS)

AF:

0.186

AC:

7375

AN:

39644

South Asian (SAS)

AF:

0.0640

AC:

5479

AN:

85550

European-Finnish (FIN)

AF:

0.00369

AC:

197

AN:

53354

Middle Eastern (MID)

AF:

0.0440

AC:

253

AN:

5752

European-Non Finnish (NFE)

AF:

0.00593

AC:

6590

AN:

1111364

Other (OTH)

AF:

0.0284

AC:

1710

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1208

2417

3625

4834

6042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.0222

AC:

3387

AN:

152274

Hom.:

159

Cov.:

AF XY:

0.0239

AC XY:

1780

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0283

AC:

1174

AN:

41546

American (AMR)

AF:

0.0121

AC:

185

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3472

East Asian (EAS)

AF:

0.220

AC:

1141

AN:

5182

South Asian (SAS)

AF:

0.0632

AC:

305

AN:

4828

European-Finnish (FIN)

AF:

0.00236

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00606

AC:

412

AN:

68036

Other (OTH)

AF:

0.0274

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

160

321

481

642

802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0166

Hom.:

463

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.090

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.045

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

PhyloP100

-0.54

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.4

REVEL

Benign

0.0090

Sift

Benign

0.34

Sift4G

Benign

0.38

Polyphen

0.0010

Vest4

0.060

MPC

0.070

ClinPred

0.0039

GERP RS

-1.6

Varity_R

0.073

gMVP

0.49

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over