6-30168441-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_033229.3(TRIM15):c.619A>T(p.Thr207Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,612,548 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (23 hom.)
• Consequence: TRIM15 NM_033229.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14

Genes affected

TRIM15 (HGNC:16284): (tripartite motif containing 15) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to the cytoplasm. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048574805).
• BP6: Variant 6-30168441-A-T is Benign according to our data. Variant chr6-30168441-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2360671.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM15	NM_033229.3	c.619A>T	p.Thr207Ser	missense_variant	3/7	ENST00000376694.9
TRIM15	XM_011514987.2	c.304A>T	p.Thr102Ser	missense_variant	4/8
TRIM15	XM_047419503.1	c.619A>T	p.Thr207Ser	missense_variant	3/5
TRIM15	XM_011514988.3	c.12A>T	p.Ser4=	synonymous_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM15	ENST00000376694.9	c.619A>T	p.Thr207Ser	missense_variant	3/7	1	NM_033229.3	P1
TRIM15	ENST00000619857.4	c.412A>T	p.Thr138Ser	missense_variant	3/8	5
TRIM15	ENST00000433744.1	c.130A>T	p.Thr44Ser	missense_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152208 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000216 AC: 53 AN: 245332 Hom.: 1 AF XY: 0.000172 AC XY: 23 AN XY: 133810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00175

Gnomad SAS exome AF: 0.0000662

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000908

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000234 AC: 341 AN: 1460222 Hom.: 23 Cov.: 32 AF XY: 0.000208 AC XY: 151 AN XY: 726406

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00149

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00422

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152326 Hom.: 5 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74492

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.000317

ExAC AF: 0.000170 AC: 20

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.19
Dann	Benign	0.82
DEOGEN2	Benign	0.0070	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
Sift4G	Benign	0.44	T;T
Polyphen		0.0	.;B
Vest4		0.035
MutPred		0.30		.;Loss of phosphorylation at T207 (P = 0.0738);
MVP		0.42
MPC		0.36
ClinPred		0.032	T
GERP RS		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.027
gMVP		0.037

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: rs369181343; hg19: chr6-30136218;