rs11466652

Variant names:

• chr4-38774682-T-A
• rs11466652
• NM_030956.4:c.909A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-38774682-T-A
• chr4-38774682-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030956.4(TLR10):​c.909A>T​(p.Lys303Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,409,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 23 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059144914).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	NM_030956.4	MANE Select	c.909A>T	p.Lys303Asn	missense	Exon 4 of 4	NP_112218.2
	TLR10	NM_001017388.3		c.909A>T	p.Lys303Asn	missense	Exon 2 of 2	NP_001017388.1
	TLR10	NM_001195106.2		c.909A>T	p.Lys303Asn	missense	Exon 3 of 3	NP_001182035.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.909A>T	p.Lys303Asn	missense	Exon 4 of 4	ENSP00000308925.4
	TLR10	ENST00000361424.6	TSL:1	c.909A>T	p.Lys303Asn	missense	Exon 2 of 2	ENSP00000354459.2
	TLR10	ENST00000506111.1	TSL:1	c.909A>T	p.Lys303Asn	missense	Exon 2 of 2	ENSP00000421483.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000486 AC: 1 AN: 205654 AF XY: 0.00000906

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1409594 Hom.: 0 Cov.: 35 AF XY: 0.00000430 AC XY: 3 AN XY: 697464

African (AFR) AF: 0.00 AC: 0 AN: 31128

American (AMR) AF: 0.00 AC: 0 AN: 33160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22850

East Asian (EAS) AF: 0.00 AC: 0 AN: 39328

South Asian (SAS) AF: 0.0000521 AC: 4 AN: 76724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5502

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091078

Other (OTH) AF: 0.00 AC: 0 AN: 58150

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.7
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Benign	0.19	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.092
MutPred		0.40		Loss of ubiquitination at K303 (P = 0.0255)
MVP		0.75
MPC		0.062
ClinPred		0.036	T
GERP RS		1.3
Varity_R		0.056
gMVP		0.30
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs11466652; hg19: chr4-38776303;