11-89710431-G-T

Position:

• chr11-89710431-G-T

Variant summary

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

The NM_001146162.1(TRIM77):​c.133G>T​(p.Asp45Tyr) 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. 9/15 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: TRIM77 NM_001146162.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.962

Genes affected

TRIM77 (HGNC:34228): (tripartite motif containing 77) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.251123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM77	NM_001146162.1	c.133G>T	p.Asp45Tyr	missense_variant	1/6	ENST00000398290.7	NP_001139634.1
TRIM77	NM_001271942.1	c.133G>T	p.Asp45Tyr	missense_variant	1/5		NP_001258871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM77	ENST00000398290.7	c.133G>T	p.Asp45Tyr	missense_variant	1/6	5	NM_001146162.1	ENSP00000474003.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Mar 16, 2024

The c.133G>T (p.D45Y) alteration is located in exon 1 (coding exon 1) of the TRIM77 gene. This alteration results from a G to T substitution at nucleotide position 133, causing the aspartic acid (D) at amino acid position 45 to be replaced by a tyrosine (Y). 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	0.14
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Uncertain	0.45	T
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.25	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.0020	D
Vest4		0.21
MVP		0.68
GERP RS		1.0
Varity_R		0.087
gMVP		0.12

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: chr11-89443599;