11-89714247-A-C

Position:

• chr11-89714247-A-C

Variant summary

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

The NM_001146162.1(TRIM77):​c.563A>C​(p.Gln188Pro) 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. 11/15 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: -1.28

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=0.07934132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM77	NM_001146162.1	c.563A>C	p.Gln188Pro	missense_variant	3/6	ENST00000398290.7	NP_001139634.1
TRIM77	NM_001271942.1	c.508-911A>C		intron_variant			NP_001258871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM77	ENST00000398290.7	c.563A>C	p.Gln188Pro	missense_variant	3/6	5	NM_001146162.1	ENSP00000474003	P1
TRIM77	ENST00000534392.4	c.157-911A>C		intron_variant		1		ENSP00000474353

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

Jul 20, 2022

The c.563A>C (p.Q188P) alteration is located in exon 3 (coding exon 3) of the TRIM77 gene. This alteration results from a A to C substitution at nucleotide position 563, causing the glutamine (Q) at amino acid position 188 to be replaced by a proline (P). 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	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.4
DANN	Benign	0.78
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.079	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.11	T
Vest4		0.16
MVP		0.16
GERP RS		0.76
Varity_R		0.25
gMVP		0.26

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: chr11-89447415;