rs1389554037

Variant names:

• chr6-41228781-C-A
• NM_198153.3:c.131C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-41228781-C-A
• chr6-41228781-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198153.3(TREML4):​c.131C>A​(p.Pro44His) 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 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P44L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TREML4 NM_198153.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22415492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREML4	NM_198153.3	c.131C>A	p.Pro44His	missense_variant	Exon 2 of 6	ENST00000341495.7	NP_937796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREML4	ENST00000341495.7	c.131C>A	p.Pro44His	missense_variant	Exon 2 of 6	1	NM_198153.3	ENSP00000342570.2
TREML4	ENST00000448827.6	c.131C>A	p.Pro44His	missense_variant	Exon 2 of 6	1		ENSP00000418078.1
TREML4	ENST00000461240.1	n.-176C>A		upstream_gene_variant		2		ENSP00000418480.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

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	0.30
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.34	.;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Benign	0.027
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.28
MutPred		0.32		Loss of glycosylation at P44 (P = 0.0174);Loss of glycosylation at P44 (P = 0.0174);
MVP		0.088
MPC		0.24
ClinPred		0.94	D
GERP RS		-0.068
Varity_R		0.37
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-41196519;