4-38774614-A-G

Variant names:

• chr4-38774614-A-G
• rs11466653
• NM_030956.4:c.977T>C

Variant summary

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

The NM_030956.4(TLR10):​c.977T>C​(p.Met326Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0412 in 1,588,362 control chromosomes in the GnomAD database, including 2,771 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.044 (305 hom., cov: 33)
  • Exomes 𝑓: 0.041 (2466 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78
• Publications: 27 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=0.0017455816).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.977T>C	p.Met326Thr	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.977T>C	p.Met326Thr	missense_variant	Exon 4 of 4	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6760 AN: 152190 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.0937

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0670

GnomAD2 exomes AF: 0.0642 AC: 14567 AN: 226738 AF XY: 0.0665

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.0739

Gnomad EAS exome AF: 0.101

Gnomad FIN exome AF: 0.0204

Gnomad NFE exome AF: 0.0321

Gnomad OTH exome AF: 0.0650

GnomAD4 exome AF: 0.0409 AC: 58733 AN: 1436054 Hom.: 2466 Cov.: 36 AF XY: 0.0444 AC XY: 31637 AN XY: 713088

African (AFR) AF: 0.0256 AC: 821 AN: 32062

American (AMR) AF: 0.137 AC: 5189 AN: 37822

Ashkenazi Jewish (ASJ) AF: 0.0789 AC: 1953 AN: 24750

East Asian (EAS) AF: 0.101 AC: 3993 AN: 39496

South Asian (SAS) AF: 0.156 AC: 12622 AN: 81050

European-Finnish (FIN) AF: 0.0230 AC: 1213 AN: 52790

Middle Eastern (MID) AF: 0.112 AC: 628 AN: 5628

European-Non Finnish (NFE) AF: 0.0264 AC: 29155 AN: 1103156

Other (OTH) AF: 0.0533 AC: 3159 AN: 59300

GnomAD4 genome AF: 0.0445 AC: 6772 AN: 152308 Hom.: 305 Cov.: 33 AF XY: 0.0471 AC XY: 3507 AN XY: 74476

African (AFR) AF: 0.0268 AC: 1115 AN: 41572

American (AMR) AF: 0.118 AC: 1809 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0838 AC: 291 AN: 3472

East Asian (EAS) AF: 0.0940 AC: 488 AN: 5190

South Asian (SAS) AF: 0.152 AC: 733 AN: 4828

European-Finnish (FIN) AF: 0.0178 AC: 189 AN: 10618

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0293 AC: 1991 AN: 68020

Other (OTH) AF: 0.0663 AC: 140 AN: 2112

Alfa AF: 0.0394 Hom.: 661

Bravo AF: 0.0486

TwinsUK AF: 0.0235 AC: 87

ALSPAC AF: 0.0291 AC: 112

ESP6500AA AF: 0.0266 AC: 117

ESP6500EA AF: 0.0278 AC: 239

ExAC AF: 0.0663 AC: 8049

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T;T;T;T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.0	.;.;.;T;.;.
MetaRNN	Benign	0.0017	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.9	M;M;M;M;M;M
PhyloP100		5.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.6	D;.;D;.;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0050	D;.;D;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Vest4		0.30
ClinPred		0.030	T
GERP RS		5.1
Varity_R		0.63
gMVP		0.42
Mutation Taster		=94/6	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: rs11466653; hg19: chr4-38776235; COSMIC: COSV58302470; COSMIC: COSV58302470;