chr1-228401056-C-T

Variant names:

• chr1-228401056-C-T
• rs558730848
• NM_145214.3:c.643G>A

Variant summary

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

The NM_145214.3(TRIM11):​c.643G>A​(p.Ala215Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,612,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: TRIM11 NM_145214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.17

Genes affected

TRIM11 (HGNC:16281): (tripartite motif containing 11) 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. This protein localizes to the nucleus and the cytoplasm. Its function has not been identified. [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=0.029768616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM11	NM_145214.3	c.643G>A	p.Ala215Thr	missense_variant	Exon 3 of 6	ENST00000284551.11	NP_660215.1
TRIM11	XM_017002412.3	c.640G>A	p.Ala214Thr	missense_variant	Exon 3 of 6		XP_016857901.1
TRIM11	XM_011544285.4	c.504+1010G>A		intron_variant	Intron 2 of 4		XP_011542587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM11	ENST00000284551.11	c.643G>A	p.Ala215Thr	missense_variant	Exon 3 of 6	1	NM_145214.3	ENSP00000284551.6

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000451 AC: 11 AN: 243968 Hom.: 0 AF XY: 0.0000376 AC XY: 5 AN XY: 133032

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000920

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1460150 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 726410

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000247

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.000149

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74496

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.000253

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.643G>A (p.A215T) alteration is located in exon 3 (coding exon 3) of the TRIM11 gene. This alteration results from a G to A substitution at nucleotide position 643, causing the alanine (A) at amino acid position 215 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	0.089
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Benign	0.80
DEOGEN2	Benign	0.016	T;T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.030	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	.;L;L
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.5	.;N;N
REVEL	Benign	0.010
Sift	Benign	0.39	.;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.067, 0.54	.;B;P
Vest4		0.18
MutPred		0.36		.;Gain of phosphorylation at A215 (P = 0.0441);Gain of phosphorylation at A215 (P = 0.0441);
MVP		0.043
MPC		0.38
ClinPred		0.026	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.053
gMVP		0.39

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: rs558730848; hg19: chr1-228588757; COSMIC: COSV52859707; COSMIC: COSV52859707;