Genetic Variant NM_001348119.1:c.1094G>C (chr17-15631636-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001348119.1(TRIM16):c.1094G>C(p.Arg365Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000737 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

TRIM16
NM_001348119.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.23

Variant links:

Genes affected

TRIM16 (HGNC:17241): (tripartite motif containing 16) The protein encoded by this gene is a tripartite motif (TRIM) family member that contains two B box domains and a coiled-coiled region that are characteristic of the B box zinc finger protein family. While it lacks a RING domain found in other TRIM proteins, the encoded protein can homodimerize or heterodimerize with other TRIM proteins and has E3 ubiquitin ligase activity. This gene is also a tumor suppressor and is involved in secretory autophagy. [provided by RefSeq, Jan 2017]

TRIM16 links:

ENSG00000251537 (HGNC:):

ENSG00000251537 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34655535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM16	NM_001348119.1 link	c.1094G>C	p.Arg365Thr	missense_variant	Exon 11 of 12	ENST00000649191.2	NP_001335048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM16	ENST00000649191.2 link	c.1094G>C	p.Arg365Thr	missense_variant	Exon 11 of 12		NM_001348119.1	ENSP00000497185.2		O95361-1
ENSG00000251537	ENST00000455584.2 link	c.1094G>C	p.Arg365Thr	missense_variant	Exon 5 of 17	2		ENSP00000402644.2		H0Y626

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000590

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251168

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000970

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000698

AC:

102

AN:

1461660

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

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:

0.0000836

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000112

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000590

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000559

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1094G>C (p.R365T) alteration is located in exon 8 (coding exon 5) of the TRIM16 gene. This alteration results from a G to C substitution at nucleotide position 1094, causing the arginine (R) at amino acid position 365 to be replaced by a threonine (T). 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

Pathogenic

0.78

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Benign

0.91

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.32

M_CAP

Benign

0.037

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.32

MVP

0.72

ClinPred

0.91

GERP RS

4.6

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