rs779588753

Variant names:

• chr4-188146822-C-A
• rs779588753
• NM_178556.5:c.857C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-188146822-C-A
• chr4-188146822-C-G
• chr4-188146822-C-T

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.857C>A​(p.Thr286Lys) variant causes a missense, splice region 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. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIML1 NM_178556.5 missense, splice_region
• Scores: Splicing: ADA: 0.0003518
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.11
• Publications: 1 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=0.18764374).

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.857C>A	p.Thr286Lys	missense splice_region	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.857C>A	p.Thr286Lys	missense splice_region	Exon 6 of 6	ENSP00000327738.3	Q8N9V2
	TRIML1	ENST00000507581.5	TSL:1	n.317C>A		splice_region non_coding_transcript_exon	Exon 3 of 3
	TRIML1	ENST00000512233.1	TSL:3	n.207C>A		splice_region non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1205434 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 579396

African (AFR) AF: 0.00 AC: 0 AN: 26150

American (AMR) AF: 0.00 AC: 0 AN: 19156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16440

East Asian (EAS) AF: 0.00 AC: 0 AN: 32096

South Asian (SAS) AF: 0.00 AC: 0 AN: 34244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4804

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 980720

Other (OTH) AF: 0.00 AC: 0 AN: 48794

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.58
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.73	N
PhyloP100		-1.1
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.14
Sift	Benign	0.25	T
Sift4G	Benign	0.93	T
Polyphen		0.22	B
Vest4		0.52
MutPred		0.57		Gain of ubiquitination at T286 (P = 0.0247)
MVP		0.26
MPC		0.061
ClinPred		0.23	T
GERP RS		4.0
Varity_R		0.12
gMVP		0.48
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00035
dbscSNV1_RF	Benign	0.042
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: rs779588753; hg19: chr4-189067976; COSMIC: COSV60194767; COSMIC: COSV60194767;