Genetic Variant TRIM16L:n.1165C>A (chr17-18734952-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The ENST00000571708.5(TRIM16L):n.1165C>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.0000155 in 1,613,288 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 0.000085 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

TRIM16L
ENST00000571708.5 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45

Variant links:

Genes affected

TRIM16L (HGNC:):

TRIM16L links:

TRIM16L (HGNC:32670): (tripartite motif containing 16 like (pseudogene)) Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRIM16L 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=0.34296393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
TRIM16L	NR_172633.1 link	n.1245C>A	non_coding_transcript_exon_variant	Exon 10 of 10
TRIM16L	NR_172634.1 link	n.1094C>A	non_coding_transcript_exon_variant	Exon 9 of 9
TRIM16L	NR_172635.1 link	n.996C>A	non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
TRIM16L	ENST00000571708.5 link	n.1165C>A	non_coding_transcript_exon_variant	Exon 10 of 10	1
TRIM16L	ENST00000414850.6 link	n.524C>A	non_coding_transcript_exon_variant	Exon 3 of 3	2
TRIM16L	ENST00000449552.6 link	n.2023C>A	non_coding_transcript_exon_variant	Exon 7 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250050

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135134

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461158

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0000224

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

AF:

0.0000855

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.539C>A (p.T180N) alteration is located in exon 5 (coding exon 4) of the TRIM16L gene. This alteration results from a C to A substitution at nucleotide position 539, causing the threonine (T) at amino acid position 180 to be replaced by an asparagine (N). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0042

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

3.1

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.14

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.020

Polyphen

0.96

Vest4

0.47

MVP

0.15

ClinPred

0.76

GERP RS

3.5

Varity_R

0.61

gMVP

0.56

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