Variant 11-89711477-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001146162.1(TRIM77):c.479G>A(p.Arg160Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,519,878 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

TRIM77
NM_001146162.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.14

Variant links:

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]

TRIM77 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01681906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM77	NM_001146162.1 linkuse as main transcript	c.479G>A	p.Arg160Lys	missense_variant	2/6	ENST00000398290.7	NP_001139634.1
TRIM77	NM_001271942.1 linkuse as main transcript	c.479G>A	p.Arg160Lys	missense_variant	2/5		NP_001258871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM77	ENST00000398290.7 linkuse as main transcript	c.479G>A	p.Arg160Lys	missense_variant	2/6	5	NM_001146162.1	ENSP00000474003	P1
TRIM77	ENST00000534392.4 linkuse as main transcript	c.128G>A	p.Arg43Lys	missense_variant	2/5	1		ENSP00000474353

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000145

AC:

AN:

131124

Hom.:

AF XY:

0.000144

AC XY:

AN XY:

69584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000349

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000611

Gnomad NFE exome

AF:

0.000208

Gnomad OTH exome

AF:

0.000273

GnomAD4 exome

AF:

0.000126

AC:

172

AN:

1367742

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

674664

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000214

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000286

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000408

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.000106

GnomAD4 genome

AF:

0.000329

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000251

Hom.:

Bravo

AF:

0.000355

ExAC

AF:

0.0000811

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.479G>A (p.R160K) alteration is located in exon 2 (coding exon 2) of the TRIM77 gene. This alteration results from a G to A substitution at nucleotide position 479, causing the arginine (R) at amino acid position 160 to be replaced by a lysine (K). 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

0.093

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.092

DANN

Benign

0.82

DEOGEN2

Benign

0.00032

T;.

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.32

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.017

T;T

MutationAssessor

Benign

-0.65

N;.

PrimateAI

Benign

0.43

Sift4G

Benign

0.51

T;T

Vest4

0.033

MVP

0.10

GERP RS

-2.9

Varity_R

0.071

gMVP

0.035

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over