rs1242967850

Variant names:

• chr4-188146857-T-C
• rs1242967850
• NM_178556.5:c.892T>C

Variant summary

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

The NM_178556.5(TRIML1):​c.892T>C​(p.Tyr298His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 1,289,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: TRIML1 NM_178556.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.46
• Publications: 0 publications found

Genes affected

TRIML1 (HGNC:26698): (tripartite motif family like 1) The protein encoded by this gene is a tripartite motif family protein with similarities to E3 ubiquitin-protein ligases. While the function of the encoded protein has not been determined, the orthologous protein in mouse has been shown to bind ubiquitin-specific protease 5 and is involved in the blastocyst development stage. [provided by RefSeq, Sep 2016]

ENSG00000247130 (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=0.07636526).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178556.5. 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
	TRIML1	NM_178556.5	MANE Select	c.892T>C	p.Tyr298His	missense	Exon 6 of 6	NP_848651.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIML1	ENST00000332517.4	TSL:1 MANE Select	c.892T>C	p.Tyr298His	missense	Exon 6 of 6	ENSP00000327738.3	Q8N9V2
	TRIML1	ENST00000507581.5	TSL:1	n.352T>C		non_coding_transcript_exon	Exon 3 of 3
	TRIML1	ENST00000512233.1	TSL:3	n.242T>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000155 AC: 2 AN: 1289116 Hom.: 0 Cov.: 31 AF XY: 0.00000160 AC XY: 1 AN XY: 625290

African (AFR) AF: 0.00 AC: 0 AN: 28486

American (AMR) AF: 0.00 AC: 0 AN: 23328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18274

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35692

South Asian (SAS) AF: 0.00 AC: 0 AN: 52200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5066

European-Non Finnish (NFE) AF: 9.75e-7 AC: 1 AN: 1026152

Other (OTH) AF: 0.00 AC: 0 AN: 52770

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000354 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.084	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-1.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.056
Sift	Benign	0.43	T
Sift4G	Benign	0.45	T
Polyphen		0.0040	B
Vest4		0.20
MVP		0.014
MPC		0.047
ClinPred		0.13	T
GERP RS		3.7
Varity_R		0.049
gMVP		0.34
Mutation Taster		=96/4	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: rs1242967850; hg19: chr4-189068011;