17-15636073-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001348119.1(TRIM16):c.812G>C(p.Arg271Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,450,176 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 28)
  • Exomes 𝑓: 0.00029 (76 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM16 NM_001348119.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.263

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040765405).
• BP6: Variant 17-15636073-C-G is Benign according to our data. Variant chr17-15636073-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2647499.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 88 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM16	NM_001348119.1	c.812G>C	p.Arg271Thr	missense_variant	9/12	ENST00000649191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM16	ENST00000649191.2	c.812G>C	p.Arg271Thr	missense_variant	9/12		NM_001348119.1	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 244 AN: 147548 Hom.: 1 Cov.: 28 FAILED QC

Gnomad AFR AF: 0.000645

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00140

Gnomad ASJ AF: 0.000589

Gnomad EAS AF: 0.00717

Gnomad SAS AF: 0.00454

Gnomad FIN AF: 0.00115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00195

Gnomad OTH AF: 0.000979

GnomAD3 exomes AF: 0.00159 AC: 387 AN: 244058 Hom.: 88 AF XY: 0.00179 AC XY: 236 AN XY: 131782

Gnomad AFR exome AF: 0.000436

Gnomad AMR exome AF: 0.000590

Gnomad ASJ exome AF: 0.000202

Gnomad EAS exome AF: 0.00551

Gnomad SAS exome AF: 0.00493

Gnomad FIN exome AF: 0.00104

Gnomad NFE exome AF: 0.000846

Gnomad OTH exome AF: 0.000995

GnomAD4 exome AF: 0.000289 AC: 419 AN: 1450176 Hom.: 76 Cov.: 32 AF XY: 0.000301 AC XY: 217 AN XY: 721366

Gnomad4 AFR exome AF: 0.000301

Gnomad4 AMR exome AF: 0.000158

Gnomad4 ASJ exome AF: 0.000154

Gnomad4 EAS exome AF: 0.00203

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.000701

Gnomad4 NFE exome AF: 0.000157

Gnomad4 OTH exome AF: 0.000284

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00168 AC: 248 AN: 147664 Hom.: 1 Cov.: 28 AF XY: 0.00160 AC XY: 115 AN XY: 72082

Gnomad4 AFR AF: 0.000742

Gnomad4 AMR AF: 0.00140

Gnomad4 ASJ AF: 0.000589

Gnomad4 EAS AF: 0.00719

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.00115

Gnomad4 NFE AF: 0.00195

Gnomad4 OTH AF: 0.000970

Alfa AF: 0.00131 Hom.: 5

ExAC AF: 0.0139 AC: 1681

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

TRIM16: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	9.1
Dann	Benign	0.29
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.57	T;T;T;.;T;T;.;T;T;T;T
MetaRNN	Benign	0.0041	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.33	T
Sift4G	Uncertain	0.022	D;D;D;D;D;D;.;T;.;T;D
Polyphen		0.0070, 0.0	.;.;B;B;.;B;B;.;.;.;.
Vest4		0.093
MPC		0.41
ClinPred		0.020	T
GERP RS		0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.094
gMVP		0.34

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

Other links and lift over

dbSNP: rs142902437; hg19: chr17-15539387; COSMIC: COSV60885564; COSMIC: COSV60885564;