rs11096957

chr4-38774870-T-G

Variant summary

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

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. 11/19 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

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=7.4726343E-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	UniProt
TLR10	NM_030956.4	c.721A>C	p.Asn241His	missense_variant	4/4	ENST00000308973.9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63429 AN: 151954 Hom.: 13865 Cov.: 33

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

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.: 38 AF XY: 0.361 AC XY: 260883 AN XY: 722578

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.: 33 AF XY: 0.418 AC XY: 31082 AN XY: 74342

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	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	19
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	N
MetaRNN	Benign	0.00075	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.6	M;M;M;M;M;M
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.38	T
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	T
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

Other links and lift over

dbSNP: rs11096957; hg19: chr4-38776491; COSMIC: COSV58300261; COSMIC: COSV58300261;