rs9998678

Variant names:

• chr4-38775899-T-A
• rs9998678
• NM_030956.4:c.-187A>T

Variant summary

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

The NM_030956.4(TLR10):​c.-187A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 225,868 control chromosomes in the GnomAD database, including 1,365 homozygotes. 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: 𝑓 0.095 (1160 hom., cov: 32)
  • Exomes 𝑓: 0.056 (205 hom.)
• Consequence: TLR10 NM_030956.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 6 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 (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 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.-187A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	NP_112218.2	Q9BXR5
	TLR10	NM_030956.4	MANE Select	c.-187A>T		5_prime_UTR	Exon 3 of 4	NP_112218.2	Q9BXR5
	TLR10	NM_001195107.2		c.-187A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	NP_001182036.1	Q9BXR5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.-187A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	ENSP00000308925.4	Q9BXR5
	TLR10	ENST00000506111.1	TSL:1	c.-187A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000421483.1	Q9BXR5
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.-187A>T		5_prime_UTR	Exon 3 of 4	ENSP00000308925.4	Q9BXR5

Frequencies

GnomAD3 genomes AF: 0.0949 AC: 14422 AN: 152036 Hom.: 1156 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0940

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0559 AC: 4118 AN: 73714 Hom.: 205 Cov.: 0 AF XY: 0.0565 AC XY: 2163 AN XY: 38304

African (AFR) AF: 0.190 AC: 447 AN: 2356

American (AMR) AF: 0.128 AC: 553 AN: 4332

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 299 AN: 2790

East Asian (EAS) AF: 0.100 AC: 532 AN: 5314

South Asian (SAS) AF: 0.133 AC: 442 AN: 3318

European-Finnish (FIN) AF: 0.0215 AC: 54 AN: 2508

Middle Eastern (MID) AF: 0.145 AC: 48 AN: 332

European-Non Finnish (NFE) AF: 0.0298 AC: 1430 AN: 48032

Other (OTH) AF: 0.0661 AC: 313 AN: 4732

GnomAD4 genome AF: 0.0949 AC: 14446 AN: 152154 Hom.: 1160 Cov.: 32 AF XY: 0.0948 AC XY: 7052 AN XY: 74390

African (AFR) AF: 0.199 AC: 8246 AN: 41436

American (AMR) AF: 0.138 AC: 2115 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3470

East Asian (EAS) AF: 0.0944 AC: 489 AN: 5178

South Asian (SAS) AF: 0.153 AC: 739 AN: 4822

European-Finnish (FIN) AF: 0.0180 AC: 191 AN: 10618

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2050 AN: 68022

Other (OTH) AF: 0.100 AC: 212 AN: 2116

Alfa AF: 0.0677 Hom.: 93

Bravo AF: 0.107

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.51
DANN	Benign	0.40
PhyloP100		-1.7
PromoterAI		-0.0055	Neutral
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: rs9998678; hg19: chr4-38777520;