NM_030956.4:c.2305G>A

Variant names:

• chr4-38773286-C-T
• rs777851196
• NM_030956.4:c.2305G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030956.4(TLR10):​c.2305G>A​(p.Ala769Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,459,936 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.750
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2305G>A	p.Ala769Thr	missense	Exon 4 of 4	NP_112218.2	Q9BXR5
	TLR10	NM_001017388.3		c.2305G>A	p.Ala769Thr	missense	Exon 2 of 2	NP_001017388.1	Q9BXR5
	TLR10	NM_001195106.2		c.2305G>A	p.Ala769Thr	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.2305G>A	p.Ala769Thr	missense	Exon 4 of 4	ENSP00000308925.4	Q9BXR5
	TLR10	ENST00000361424.6	TSL:1	c.2305G>A	p.Ala769Thr	missense	Exon 2 of 2	ENSP00000354459.2	Q9BXR5
	TLR10	ENST00000506111.1	TSL:1	c.2305G>A	p.Ala769Thr	missense	Exon 2 of 2	ENSP00000421483.1	Q9BXR5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248706 AF XY: 0.0000149

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: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1459936 Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5 AN XY: 726252

African (AFR) AF: 0.00 AC: 0 AN: 33324

American (AMR) AF: 0.00 AC: 0 AN: 44186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 85774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111450

Other (OTH) AF: 0.0000166 AC: 1 AN: 60306

GnomAD4 genome Cov.: 32

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.050
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.57	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.75
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.17
MutPred		0.52		Gain of MoRF binding (P = 0.1271)
MVP		0.90
MPC		0.061
ClinPred		0.86	D
GERP RS		3.8
Varity_R		0.83
gMVP		0.037
Mutation Taster		=55/45	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: rs777851196; hg19: chr4-38774907;