4-188139758-C-T

Variant names:

• chr4-188139758-C-T
• NM_178556.5:c.200C>T

Variant summary

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

The NM_178556.5(TRIML1):​c.200C>T​(p.Ser67Leu) variant causes a missense 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. 15/21 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)
• Consequence: TRIML1 NM_178556.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.245

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]

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=0.12359011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIML1	NM_178556.5	c.200C>T	p.Ser67Leu	missense_variant	Exon 1 of 6	ENST00000332517.4	NP_848651.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIML1	ENST00000332517.4	c.200C>T	p.Ser67Leu	missense_variant	Exon 1 of 6	1	NM_178556.5	ENSP00000327738.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.200C>T (p.S67L) alteration is located in exon 1 (coding exon 1) of the TRIML1 gene. This alteration results from a C to T substitution at nucleotide position 200, causing the serine (S) at amino acid position 67 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.30
Sift	Benign	0.13	T
Sift4G	Benign	0.56	T
Polyphen		0.0030	B
Vest4		0.099
MutPred		0.28		Loss of disorder (P = 0.0236);
MVP		0.65
MPC		0.033
ClinPred		0.20	T
GERP RS		4.7
Varity_R		0.11
gMVP		0.47

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: chr4-189060912;