rs750785182

Variant names:

• chr6-41228961-C-G
• rs750785182
• NM_198153.3:c.311C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-41228961-C-G
• chr6-41228961-C-T

Variant summary

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

The NM_198153.3(TREML4):​c.311C>G​(p.Ser104Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S104L) 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: -0.237
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.311C>G	p.Ser104Trp	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.311C>G	p.Ser104Trp	missense	Exon 2 of 6	ENSP00000342570.2	Q6UXN2
	TREML4	ENST00000448827.6	TSL:1	c.311C>G	p.Ser104Trp	missense	Exon 2 of 6	ENSP00000418078.1	Q6UXN2
	ENSG00000290563	ENST00000564680.6	TSL:1	n.206-10967G>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	Pathogenic	0.64
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.24
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.65		Loss of glycosylation at S104 (P = 0.0142)
MVP		0.35
MPC		0.23
ClinPred		0.74	D
GERP RS		-0.36
Varity_R		0.67
gMVP		0.54
Mutation Taster		=92/8	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: rs750785182; hg19: chr6-41196699; COSMIC: COSV58384757;