4-38773336-T-G

Variant names:

• chr4-38773336-T-G
• NM_030956.4:c.2255A>C

Variant summary

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

The NM_030956.4(TLR10):​c.2255A>C​(p.Lys752Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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=0.26687163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.2255A>C	p.Lys752Thr	missense_variant	Exon 4 of 4	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.2255A>C	p.Lys752Thr	missense_variant	Exon 4 of 4	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461626 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;T;T;T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.94	.;.;.;D;.;.
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.27	T;T;T;T;T;T
MetaSVM	Uncertain	-0.097	T
MutationAssessor	Uncertain	2.3	M;M;M;M;M;M
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.0	D;.;D;.;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;.;D;.;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D
Polyphen		0.26	B;B;B;B;B;B
Vest4		0.23
MutPred		0.55		Loss of ubiquitination at K752 (P = 0.0496);Loss of ubiquitination at K752 (P = 0.0496);Loss of ubiquitination at K752 (P = 0.0496);Loss of ubiquitination at K752 (P = 0.0496);Loss of ubiquitination at K752 (P = 0.0496);Loss of ubiquitination at K752 (P = 0.0496);
MVP		0.90
MPC		0.32
ClinPred		0.98	D
GERP RS		2.7
Varity_R		0.42
gMVP		0.098

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-38774957;