11-55888132-A-C

Position:

• chr11-55888132-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032681.4(TRIM51):​c.608A>C​(p.Lys203Thr) 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. 12/20 in silico tools predict a benign 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.)
  • Failed GnomAD Quality Control
• Consequence: TRIM51 NM_032681.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

Genes affected

TRIM51 (HGNC:19023): (tripartite motif-containing 51) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1359519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM51	NM_032681.4	c.608A>C	p.Lys203Thr	missense_variant	4/7	ENST00000449290.6	NP_116070.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM51	ENST00000449290.6	c.608A>C	p.Lys203Thr	missense_variant	4/7	5	NM_032681.4	ENSP00000395086.2
TRIM51	ENST00000244891.3	c.179A>C	p.Lys60Thr	missense_variant	2/5	1		ENSP00000244891.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1461402 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727010

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: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2022

The c.608A>C (p.K203T) alteration is located in exon 4 (coding exon 3) of the TRIM51 gene. This alteration results from a A to C substitution at nucleotide position 608, causing the lysine (K) at amino acid position 203 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.5
DANN	Benign	0.97
DEOGEN2	Benign	0.061	T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.00084	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.050
Sift	Uncertain	0.0050	D;T
Sift4G	Uncertain	0.013	D;D
Polyphen		0.14	B;.
Vest4		0.20
MutPred		0.53		Loss of ubiquitination at K203 (P = 0.0092);.;
MVP		0.18
MPC		0.12
ClinPred		0.25	T
GERP RS		-0.81
Varity_R		0.15
gMVP		0.065

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-55655608;