NM_030956.4:c.2323A>G

Variant names:

• chr4-38773268-T-C
• rs4129009
• NM_030956.4:c.2323A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030956.4(TLR10):​c.2323A>G​(p.Ile775Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,611,796 control chromosomes in the GnomAD database, including 23,983 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 0.14 (1872 hom., cov: 32)
  • Exomes 𝑓: 0.16 (22111 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 89 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005084753).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	NM_030956.4	MANE Select	c.2323A>G	p.Ile775Val	missense	Exon 4 of 4	NP_112218.2
	TLR10	NM_001017388.3		c.2323A>G	p.Ile775Val	missense	Exon 2 of 2	NP_001017388.1
	TLR10	NM_001195106.2		c.2323A>G	p.Ile775Val	missense	Exon 3 of 3	NP_001182035.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.2323A>G	p.Ile775Val	missense	Exon 4 of 4	ENSP00000308925.4
	TLR10	ENST00000361424.6	TSL:1	c.2323A>G	p.Ile775Val	missense	Exon 2 of 2	ENSP00000354459.2
	TLR10	ENST00000506111.1	TSL:1	c.2323A>G	p.Ile775Val	missense	Exon 2 of 2	ENSP00000421483.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20588 AN: 152064 Hom.: 1872 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.168 AC: 41690 AN: 248768 AF XY: 0.175

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.265

Gnomad FIN exome AF: 0.0812

Gnomad NFE exome AF: 0.190

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.164 AC: 239772 AN: 1459614 Hom.: 22111 Cov.: 35 AF XY: 0.167 AC XY: 121121 AN XY: 726070

African (AFR) AF: 0.0285 AC: 950 AN: 33338

American (AMR) AF: 0.120 AC: 5303 AN: 44126

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 6931 AN: 26026

East Asian (EAS) AF: 0.346 AC: 13747 AN: 39692

South Asian (SAS) AF: 0.189 AC: 16213 AN: 85694

European-Finnish (FIN) AF: 0.0837 AC: 4467 AN: 53382

Middle Eastern (MID) AF: 0.254 AC: 1465 AN: 5762

European-Non Finnish (NFE) AF: 0.163 AC: 181166 AN: 1111312

Other (OTH) AF: 0.158 AC: 9530 AN: 60282

GnomAD4 genome AF: 0.135 AC: 20580 AN: 152182 Hom.: 1872 Cov.: 32 AF XY: 0.132 AC XY: 9856 AN XY: 74416

African (AFR) AF: 0.0316 AC: 1312 AN: 41548

American (AMR) AF: 0.168 AC: 2570 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1421 AN: 5154

South Asian (SAS) AF: 0.177 AC: 851 AN: 4820

European-Finnish (FIN) AF: 0.0781 AC: 828 AN: 10604

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11926 AN: 67978

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.177 Hom.: 8394

Bravo AF: 0.141

TwinsUK AF: 0.171 AC: 633

ALSPAC AF: 0.188 AC: 726

ESP6500AA AF: 0.0293 AC: 129

ESP6500EA AF: 0.173 AC: 1492

ExAC AF: 0.174 AC: 21106

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.14
DANN	Benign	0.28
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.34
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.043
Sift	Benign	0.23	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.047
ClinPred		0.00030	T
GERP RS		-5.3
Varity_R		0.12
gMVP		0.062
Mutation Taster		=95/5	polymorphism (auto)

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: rs4129009; hg19: chr4-38774889; COSMIC: COSV58301605; COSMIC: COSV58301605;