4-38773456-A-T

Position:

• chr4-38773456-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030956.4(TLR10):​c.2135T>A​(p.Phe712Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.12

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42116666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR10	NM_030956.4	c.2135T>A	p.Phe712Tyr	missense_variant	4/4	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.2135T>A	p.Phe712Tyr	missense_variant	4/4	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2024

The c.2135T>A (p.F712Y) alteration is located in exon 4 (coding exon 1) of the TLR10 gene. This alteration results from a T to A substitution at nucleotide position 2135, causing the phenylalanine (F) at amino acid position 712 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T;T;T;T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	.;.;.;D;.;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.42	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M;M;M;M;M;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.6	D;.;D;.;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;.;D;.;D;D
Sift4G	Uncertain	0.019	D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;D;D
Vest4		0.34
MutPred		0.59		Loss of catalytic residue at F712 (P = 0.1081);Loss of catalytic residue at F712 (P = 0.1081);Loss of catalytic residue at F712 (P = 0.1081);Loss of catalytic residue at F712 (P = 0.1081);Loss of catalytic residue at F712 (P = 0.1081);Loss of catalytic residue at F712 (P = 0.1081);
MVP		0.43
MPC		0.30
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.74
gMVP		0.069

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-38775077;