17-15628628-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001348119.1(TRIM16):c.1682G>T(p.Gly561Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,607,676 control chromosomes in the GnomAD database, including 48,021 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.23 (4119 hom., cov: 31)
  • Exomes 𝑓: 0.24 (43902 hom.)
• Consequence: TRIM16 NM_001348119.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.439

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004581034).
• BP6: Variant 17-15628628-C-A is Benign according to our data. Variant chr17-15628628-C-A is described in ClinVar as [Benign]. Clinvar id is 770442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM16	NM_001348119.1	c.1682G>T	p.Gly561Val	missense_variant	12/12	ENST00000649191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM16	ENST00000649191.2	c.1682G>T	p.Gly561Val	missense_variant	12/12		NM_001348119.1	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34695 AN: 151822 Hom.: 4112 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.247 AC: 58703 AN: 237998 Hom.: 7403 AF XY: 0.246 AC XY: 31757 AN XY: 129044

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.326

Gnomad SAS exome AF: 0.272

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.229

GnomAD4 exome AF: 0.245 AC: 356061 AN: 1455734 Hom.: 43902 Cov.: 32 AF XY: 0.245 AC XY: 177244 AN XY: 723774

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.229 AC: 34720 AN: 151942 Hom.: 4119 Cov.: 31 AF XY: 0.228 AC XY: 16964 AN XY: 74256

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.227

Alfa AF: 0.188 Hom.: 685

Bravo AF: 0.229

ExAC AF: 0.238 AC: 28829

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	0.66
Dann	Benign	0.73
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.28	T;T;.;T;.
MetaRNN	Benign	0.0046	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P
Sift4G	Benign	0.16	T;T;T;T;.
Polyphen		0.037, 0.0040	.;B;B;B;B
Vest4		0.050
MPC		0.17
ClinPred		0.00071	T
GERP RS		0.87
Varity_R		0.035
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1060903; hg19: chr17-15531942; COSMIC: COSV60885756; COSMIC: COSV60885756;