NM_030956.4:c.721A>C

Variant names:

• chr4-38774870-T-G
• rs11096957
• NM_030956.4:c.721A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030956.4(TLR10):​c.721A>C​(p.Asn241His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,605,706 control chromosomes in the GnomAD database, including 110,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (13903 hom., cov: 33)
  • Exomes 𝑓: 0.35 (96826 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 111 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.4726343E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

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.721A>C	p.Asn241His	missense	Exon 4 of 4	NP_112218.2	Q9BXR5
	TLR10	NM_001017388.3		c.721A>C	p.Asn241His	missense	Exon 2 of 2	NP_001017388.1	Q9BXR5
	TLR10	NM_001195106.2		c.721A>C	p.Asn241His	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.721A>C	p.Asn241His	missense	Exon 4 of 4	ENSP00000308925.4	Q9BXR5
	TLR10	ENST00000361424.6	TSL:1	c.721A>C	p.Asn241His	missense	Exon 2 of 2	ENSP00000354459.2	Q9BXR5
	TLR10	ENST00000506111.1	TSL:1	c.721A>C	p.Asn241His	missense	Exon 2 of 2	ENSP00000421483.1	Q9BXR5

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63429 AN: 151954 Hom.: 13865 Cov.: 33

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.473

GnomAD2 exomes AF: 0.416 AC: 101773 AN: 244642 AF XY: 0.425

Gnomad AFR exome AF: 0.518

Gnomad AMR exome AF: 0.344

Gnomad ASJ exome AF: 0.494

Gnomad EAS exome AF: 0.533

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.421

GnomAD4 exome AF: 0.352 AC: 511998 AN: 1453632 Hom.: 96826 Cov.: 38 AF XY: 0.361 AC XY: 260883 AN XY: 722578

African (AFR) AF: 0.528 AC: 17448 AN: 33018

American (AMR) AF: 0.354 AC: 15289 AN: 43146

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 12826 AN: 25822

East Asian (EAS) AF: 0.573 AC: 22699 AN: 39614

South Asian (SAS) AF: 0.562 AC: 47690 AN: 84828

European-Finnish (FIN) AF: 0.344 AC: 18285 AN: 53172

Middle Eastern (MID) AF: 0.600 AC: 3440 AN: 5734

European-Non Finnish (NFE) AF: 0.317 AC: 351502 AN: 1108302

Other (OTH) AF: 0.380 AC: 22819 AN: 59996

GnomAD4 genome AF: 0.418 AC: 63504 AN: 152074 Hom.: 13903 Cov.: 33 AF XY: 0.418 AC XY: 31082 AN XY: 74342

African (AFR) AF: 0.516 AC: 21418 AN: 41476

American (AMR) AF: 0.411 AC: 6283 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1736 AN: 3462

East Asian (EAS) AF: 0.534 AC: 2762 AN: 5174

South Asian (SAS) AF: 0.547 AC: 2639 AN: 4828

European-Finnish (FIN) AF: 0.345 AC: 3649 AN: 10574

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23486 AN: 67966

Other (OTH) AF: 0.473 AC: 1001 AN: 2116

Alfa AF: 0.388 Hom.: 42597

Bravo AF: 0.423

TwinsUK AF: 0.316 AC: 1170

ALSPAC AF: 0.336 AC: 1294

ESP6500AA AF: 0.506 AC: 2231

ESP6500EA AF: 0.343 AC: 2951

ExAC AF: 0.428 AC: 51977

Asia WGS AF: 0.514 AC: 1791 AN: 3478

EpiCase AF: 0.365

EpiControl AF: 0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.017
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.00075	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.3
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.29
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.86	P
Vest4		0.15
MPC		0.25
ClinPred		0.052	T
GERP RS		4.9
Varity_R		0.17
gMVP		0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs11096957; hg19: chr4-38776491; COSMIC: COSV58300261; COSMIC: COSV58300261;