chr4-38773259-T-C

Variant names:

• chr4-38773259-T-C
• rs755738760
• NM_030956.4:c.2332A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030956.4(TLR10):​c.2332A>G​(p.Asn778Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,904 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.992
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05699116).

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.2332A>G	p.Asn778Asp	missense	Exon 4 of 4	NP_112218.2	Q9BXR5
	TLR10	NM_001017388.3		c.2332A>G	p.Asn778Asp	missense	Exon 2 of 2	NP_001017388.1	Q9BXR5
	TLR10	NM_001195106.2		c.2332A>G	p.Asn778Asp	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.2332A>G	p.Asn778Asp	missense	Exon 4 of 4	ENSP00000308925.4	Q9BXR5
	TLR10	ENST00000361424.6	TSL:1	c.2332A>G	p.Asn778Asp	missense	Exon 2 of 2	ENSP00000354459.2	Q9BXR5
	TLR10	ENST00000506111.1	TSL:1	c.2332A>G	p.Asn778Asp	missense	Exon 2 of 2	ENSP00000421483.1	Q9BXR5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000282 AC: 7 AN: 248184 AF XY: 0.0000224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000383

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1458904 Hom.: 0 Cov.: 34 AF XY: 0.00000689 AC XY: 5 AN XY: 725686

African (AFR) AF: 0.00 AC: 0 AN: 33290

American (AMR) AF: 0.00 AC: 0 AN: 43948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25982

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 85572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111054

Other (OTH) AF: 0.00 AC: 0 AN: 60244

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions as Germline

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	0.088
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.3
DANN	Benign	0.84
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.99
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.052
Sift	Benign	0.18	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.51		Gain of loop (P = 0.024)
MVP		0.26
MPC		0.059
ClinPred		0.031	T
GERP RS		2.8
Varity_R		0.094
gMVP		0.063
Mutation Taster		=99/1	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: rs755738760; hg19: chr4-38774880;