4-188139622-T-C

Position:

• chr4-188139622-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000332517.4(TRIML1):​c.64T>C​(p.Tyr22His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIML1 ENST00000332517.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.227

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]

TRIML1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33788878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIML1	NM_178556.5	c.64T>C	p.Tyr22His	missense_variant	1/6	ENST00000332517.4	NP_848651.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIML1	ENST00000332517.4	c.64T>C	p.Tyr22His	missense_variant	1/6	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.64T>C (p.Y22H) alteration is located in exon 1 (coding exon 1) of the TRIML1 gene. This alteration results from a T to C substitution at nucleotide position 64, causing the tyrosine (Y) at amino acid position 22 to be replaced by a histidine (H). 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	Pathogenic	0.68
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	0.60	N
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.56		Loss of glycosylation at S25 (P = 0.0491);
MVP		0.36
MPC		0.28
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.79
gMVP		0.45

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: chr4-189060776;