4-38773195-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_030956.4(TLR10):c.2396G>A(p.Arg799Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,554,818 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R799L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (32 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.865

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044157505).
• BP6: Variant 4-38773195-C-T is Benign according to our data. Variant chr4-38773195-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR10	NM_030956.4	c.2396G>A	p.Arg799Gln	missense_variant	4/4	ENST00000308973.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR10	ENST00000308973.9	c.2396G>A	p.Arg799Gln	missense_variant	4/4	5	NM_030956.4	P1

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 561 AN: 152150 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00501

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00441 AC: 874 AN: 198028 Hom.: 10 AF XY: 0.00472 AC XY: 496 AN XY: 105082

Gnomad AFR exome AF: 0.000384

Gnomad AMR exome AF: 0.00430

Gnomad ASJ exome AF: 0.0195

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00726

Gnomad FIN exome AF: 0.000594

Gnomad NFE exome AF: 0.00509

Gnomad OTH exome AF: 0.00737

GnomAD4 exome AF: 0.00352 AC: 4930 AN: 1402550 Hom.: 32 Cov.: 34 AF XY: 0.00375 AC XY: 2601 AN XY: 693042

Gnomad4 AFR exome AF: 0.000512

Gnomad4 AMR exome AF: 0.00402

Gnomad4 ASJ exome AF: 0.0166

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00845

Gnomad4 FIN exome AF: 0.000746

Gnomad4 NFE exome AF: 0.00309

Gnomad4 OTH exome AF: 0.00551

GnomAD4 genome AF: 0.00368 AC: 560 AN: 152268 Hom.: 2 Cov.: 32 AF XY: 0.00359 AC XY: 267 AN XY: 74454

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00501

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00531 Hom.: 11

Bravo AF: 0.00375

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00651 AC: 56

ExAC AF: 0.00492 AC: 596

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

TLR10: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.51
Dann	Benign	0.67
DEOGEN2	Benign	0.019	T;T;T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0097	N
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.0044	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L;L;L;L;L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.27	N;.;N;.;N;N
REVEL	Benign	0.014
Sift	Benign	0.29	T;.;T;.;T;T
Sift4G	Benign	0.77	T;T;T;T;T;T
Polyphen		0.0070	B;B;B;B;B;B
Vest4		0.066
MVP		0.19
MPC		0.060
ClinPred		0.0026	T
GERP RS		-1.6
Varity_R		0.025
gMVP		0.15

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: rs4129008; hg19: chr4-38774816;