NM_198153.3:c.221C>G

Variant names:

• chr6-41228871-C-G
• rs1372278241
• NM_198153.3:c.221C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198153.3(TREML4):​c.221C>G​(p.Thr74Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T74K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TREML4 NM_198153.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 0 publications found

Genes affected

TREML4 (HGNC:30807): (triggering receptor expressed on myeloid cells like 4) Predicted to enable signaling receptor activity. Involved in positive regulation of toll-like receptor 7 signaling pathway. Predicted to be located in endoplasmic reticulum. Predicted to be active in cell surface. Predicted to colocalize with endosome membrane and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000290563 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20239684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198153.3. 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
	TREML4	NM_198153.3	MANE Select	c.221C>G	p.Thr74Arg	missense	Exon 2 of 6	NP_937796.1	Q6UXN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREML4	ENST00000341495.7	TSL:1 MANE Select	c.221C>G	p.Thr74Arg	missense	Exon 2 of 6	ENSP00000342570.2	Q6UXN2
	TREML4	ENST00000448827.6	TSL:1	c.221C>G	p.Thr74Arg	missense	Exon 2 of 6	ENSP00000418078.1	Q6UXN2
	ENSG00000290563	ENST00000564680.6	TSL:1	n.206-10877G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.2
DANN	Benign	0.95
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.93	L
PhyloP100		-2.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.088
Sift	Benign	0.21	T
Sift4G	Benign	0.20	T
Polyphen		0.85	P
Vest4		0.11
MutPred		0.41		Gain of MoRF binding (P = 0.0044)
MVP		0.099
MPC		0.077
ClinPred		0.27	T
GERP RS		-1.4
Varity_R		0.17
gMVP		0.21
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: rs1372278241; hg19: chr6-41196609;