chr6-30171922-G-C

Position:

• chr6-30171922-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033229.3(TRIM15):​c.971G>C​(p.Ser324Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S324N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM15 NM_033229.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05360657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM15	NM_033229.3	c.971G>C	p.Ser324Thr	missense_variant	7/7	ENST00000376694.9	NP_150232.2
TRIM15	XM_011514987.2	c.656G>C	p.Ser219Thr	missense_variant	8/8		XP_011513289.1
TRIM15	XM_011514988.3	c.350G>C	p.Ser117Thr	missense_variant	5/5		XP_011513290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM15	ENST00000376694.9	c.971G>C	p.Ser324Thr	missense_variant	7/7	1	NM_033229.3	ENSP00000365884.4
TRIM15	ENST00000619857.4	c.764G>C	p.Ser255Thr	missense_variant	8/8	5		ENSP00000484001.1
TRIM15	ENST00000433744.1	c.456G>C	p.Glu152Asp	missense_variant	5/5	3		ENSP00000398285.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1445460 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 717654

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.68
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.15	N
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.98	.;N
REVEL	Benign	0.014
Sift	Benign	0.076	.;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0	.;B
Vest4		0.032
MutPred		0.21		.;Loss of MoRF binding (P = 0.1185);
MVP		0.25
MPC		0.36
ClinPred		0.038	T
GERP RS		0.83
Varity_R		0.051
gMVP		0.057

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: rs929156; hg19: chr6-30139699;