17-15628882-G-C

Variant names:

• chr17-15628882-G-C
• rs1285555000
• NM_001348119.1:c.1428C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001348119.1(TRIM16):​c.1428C>G​(p.Phe476Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRIM16 NM_001348119.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61
• Publications: 0 publications found

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]

ENSG00000251537 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM16	NM_001348119.1	MANE Select	c.1428C>G	p.Phe476Leu	missense	Exon 12 of 12	NP_001335048.1	O95361-1
	TRIM16	NM_001348120.1		c.1428C>G	p.Phe476Leu	missense	Exon 10 of 10	NP_001335049.1	O95361-1
	TRIM16	NM_006470.4		c.1428C>G	p.Phe476Leu	missense	Exon 9 of 9	NP_006461.3	O95361-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM16	ENST00000649191.2	MANE Select	c.1428C>G	p.Phe476Leu	missense	Exon 12 of 12	ENSP00000497185.2	O95361-1
	TRIM16	ENST00000336708.11	TSL:1	c.1428C>G	p.Phe476Leu	missense	Exon 9 of 9	ENSP00000338989.7	O95361-1
	TRIM16	ENST00000577886.5	TSL:1	c.780C>G	p.Phe260Leu	missense	Exon 5 of 5	ENSP00000462903.1	O95361-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251474 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.6
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.013	D
Polyphen		0.95	P
Vest4		0.23
MutPred		0.76		Loss of ubiquitination at K474 (P = 0.0777)
MVP		0.72
MPC		0.57
ClinPred		0.94	D
GERP RS		3.7
Varity_R		0.37
gMVP		0.57

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

Other links and lift over

dbSNP: rs1285555000; hg19: chr17-15532196;