4-38773195-C-T

Variant names:

• chr4-38773195-C-T
• rs4129008
• NM_030956.4:c.2396G>A

Variant summary

Our verdict is Benign. The variant received -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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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
• Publications: 17 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 -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 VariationId is 2654723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.2396G>A	p.Arg799Gln	missense	Exon 4 of 4	NP_112218.2	Q9BXR5
	TLR10	NM_001017388.3		c.2396G>A	p.Arg799Gln	missense	Exon 2 of 2	NP_001017388.1	Q9BXR5
	TLR10	NM_001195106.2		c.2396G>A	p.Arg799Gln	missense	Exon 3 of 3	NP_001182035.1	Q9BXR5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.2396G>A	p.Arg799Gln	missense	Exon 4 of 4	ENSP00000308925.4	Q9BXR5
	TLR10	ENST00000361424.6	TSL:1	c.2396G>A	p.Arg799Gln	missense	Exon 2 of 2	ENSP00000354459.2	Q9BXR5
	TLR10	ENST00000506111.1	TSL:1	c.2396G>A	p.Arg799Gln	missense	Exon 2 of 2	ENSP00000421483.1	Q9BXR5

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

GnomAD2 exomes AF: 0.00441 AC: 874 AN: 198028 AF XY: 0.00472

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 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

African (AFR) AF: 0.000512 AC: 16 AN: 31238

American (AMR) AF: 0.00402 AC: 137 AN: 34098

Ashkenazi Jewish (ASJ) AF: 0.0166 AC: 362 AN: 21862

East Asian (EAS) AF: 0.00 AC: 0 AN: 39416

South Asian (SAS) AF: 0.00845 AC: 626 AN: 74092

European-Finnish (FIN) AF: 0.000746 AC: 38 AN: 50948

Middle Eastern (MID) AF: 0.0134 AC: 73 AN: 5464

European-Non Finnish (NFE) AF: 0.00309 AC: 3359 AN: 1087560

Other (OTH) AF: 0.00551 AC: 319 AN: 57872

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

African (AFR) AF: 0.000409 AC: 17 AN: 41556

American (AMR) AF: 0.00399 AC: 61 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4828

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00501 AC: 341 AN: 68016

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00500 Hom.: 15

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

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.86
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.014
Sift	Benign	0.29	T
Sift4G	Benign	0.77	T
Polyphen		0.0070	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
Mutation Taster		=100/0	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: rs4129008; hg19: chr4-38774816; COSMIC: COSV107356002; COSMIC: COSV107356002;