rs145034109

Variant names:

• chr6-41192449-T-A
• NM_024807.4:c.944A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-41192449-T-A
• chr6-41192449-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024807.4(TREML2):​c.944A>T​(p.Tyr315Phe) 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 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TREML2 NM_024807.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

Genes affected

TREML2 (HGNC:21092): (triggering receptor expressed on myeloid cells like 2) TREML2 is located in a gene cluster on chromosome 6 with the single Ig variable (IgV) domain activating receptors TREM1 (MIM 605085) and TREM2 (MIM 605086), but it has distinct structural and functional properties (Allcock et al., 2003 [PubMed 12645956]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052755058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREML2	NM_024807.4	c.944A>T	p.Tyr315Phe	missense_variant	Exon 5 of 5	ENST00000483722.2	NP_079083.2
TREML2	XM_011514917.3	c.623A>T	p.Tyr208Phe	missense_variant	Exon 4 of 4		XP_011513219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREML2	ENST00000483722.2	c.944A>T	p.Tyr315Phe	missense_variant	Exon 5 of 5	1	NM_024807.4	ENSP00000418767.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461688 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

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	0.082
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.4
DANN	Benign	0.39
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.0030
Sift	Benign	0.10	T
Sift4G	Benign	0.46	T
Polyphen		0.012	B
Vest4		0.13
MutPred		0.32		Loss of phosphorylation at Y315 (P = 0.0288);
MVP		0.014
MPC		0.19
ClinPred		0.031	T
GERP RS		0.16
Varity_R		0.12
gMVP		0.051

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: chr6-41160187;