4-38774486-T-G

Variant names:

• chr4-38774486-T-G
• rs11096955
• NM_030956.4:c.1105A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I369T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.42 (13913 hom., cov: 32)
  • Exomes 𝑓: 0.35 (95635 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577

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]

ACMG classification

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 rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.1105A>C	p.Ile369Leu	missense_variant	Exon 4 of 4	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.1105A>C	p.Ile369Leu	missense_variant	Exon 4 of 4	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63424 AN: 151922 Hom.: 13875 Cov.: 32

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

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.: 37 AF XY: 0.360 AC XY: 258378 AN XY: 717960

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.: 32 AF XY: 0.418 AC XY: 31079 AN XY: 74330

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	T
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	N
LIST_S2	Benign	0.21	.;.;.;T;.;.
MetaRNN	Benign	0.000071	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N;N;N;N;N;N
PrimateAI	Benign	0.27	T
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	T
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

Other links and lift over

dbSNP: rs11096955; hg19: chr4-38776107; COSMIC: COSV58300511; COSMIC: COSV58300511;