rs180844753

Variant names:

• chr4-188139614-G-A
• NM_178556.5:c.56G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-188139614-G-A
• chr4-188139614-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_178556.5(TRIML1):​c.56G>A​(p.Cys19Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: TRIML1 NM_178556.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.92

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIML1	NM_178556.5	c.56G>A	p.Cys19Tyr	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.56G>A	p.Cys19Tyr	missense_variant	Exon 1 of 6	1	NM_178556.5	ENSP00000327738.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461090 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726806

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: 9.00e-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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.99
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Pathogenic	4.8	H
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-9.6	D
REVEL	Pathogenic	0.65
Sift	Benign	0.085	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.90		Gain of catalytic residue at L14 (P = 0.0666);
MVP		0.67
MPC		0.29
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.89
gMVP		0.80

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: chr4-189060768;