Variant chr1-228408396-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000366698.7(TRIM17):c.1239G>C(p.Glu413Asp) 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. 16/21 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM17
ENST00000366698.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0170

Variant links:

Genes affected

TRIM17 (HGNC:13430): (tripartite motif containing 17) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. The protein is expressed almost exclusively in the testis, but its function is unknown. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

TRIM17 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.24990141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM17	NM_016102.4 linkuse as main transcript	c.1239G>C	p.Glu413Asp	missense_variant	7/7	ENST00000366698.7	NP_057186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM17	ENST00000366698.7 linkuse as main transcript	c.1239G>C	p.Glu413Asp	missense_variant	7/7	1	NM_016102.4	ENSP00000355659	P1	Q9Y577-1
	ENST00000701501.1 linkuse as main transcript	n.283+918C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 17, 2022

The c.1239G>C (p.E413D) alteration is located in exon 7 (coding exon 6) of the TRIM17 gene. This alteration results from a G to C substitution at nucleotide position 1239, causing the glutamic acid (E) at amino acid position 413 to be replaced by an aspartic acid (D). 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

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.064

M_CAP

Benign

0.014

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.44

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.54

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.22

MutPred

0.44

Loss of catalytic residue at E413 (P = 0.0145);Loss of catalytic residue at E413 (P = 0.0145);Loss of catalytic residue at E413 (P = 0.0145);

MVP

0.76

MPC

0.38

ClinPred

0.21

GERP RS

3.0

Varity_R

0.061

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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