Genetic Variant TRIM16:p.Leu518Val (chr17-15628758-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001348119.1(TRIM16):c.1552C>G(p.Leu518Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TRIM16
NM_001348119.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348119.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM16	NM_001348119.1	MANE Select	c.1552C>G	p.Leu518Val	missense	Exon 12 of 12	NP_001335048.1	O95361-1
TRIM16	NM_001348120.1		c.1552C>G	p.Leu518Val	missense	Exon 10 of 10	NP_001335049.1	O95361-1
TRIM16	NM_006470.4		c.1552C>G	p.Leu518Val	missense	Exon 9 of 9	NP_006461.3	O95361-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM16	ENST00000649191.2	MANE Select	c.1552C>G	p.Leu518Val	missense	Exon 12 of 12	ENSP00000497185.2	O95361-1
TRIM16	ENST00000336708.11	TSL:1	c.1552C>G	p.Leu518Val	missense	Exon 9 of 9	ENSP00000338989.7	O95361-1
TRIM16	ENST00000577886.5	TSL:1	c.904C>G	p.Leu302Val	missense	Exon 5 of 5	ENSP00000462903.1	O95361-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251494

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.70

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.74

MetaSVM

Uncertain

-0.054

MutationAssessor

Pathogenic

3.0

PhyloP100

4.9

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.40

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.033

Polyphen

1.0

Vest4

0.41

MutPred

0.72

Gain of glycosylation at T517 (P = 0.0998)

MVP

0.68

MPC

0.55

ClinPred

0.92

GERP RS

4.7

Varity_R

0.26

gMVP

0.39

Mutation Taster

=59/41

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over