NM_145214.3:c.1025A>G

Variant names:

• chr1-228395087-T-C
• NM_145214.3:c.1025A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_145214.3(TRIM11):​c.1025A>G​(p.His342Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM11 NM_145214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11

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]

ENSG00000270094 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM11	NM_145214.3	c.1025A>G	p.His342Arg	missense_variant	Exon 6 of 6	ENST00000284551.11	NP_660215.1
TRIM11	XM_017002412.3	c.1022A>G	p.His341Arg	missense_variant	Exon 6 of 6		XP_016857901.1
TRIM11	XM_011544285.4	c.794A>G	p.His265Arg	missense_variant	Exon 5 of 5		XP_011542587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM11	ENST00000284551.11	c.1025A>G	p.His342Arg	missense_variant	Exon 6 of 6	1	NM_145214.3	ENSP00000284551.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1025A>G (p.H342R) alteration is located in exon 6 (coding exon 6) of the TRIM11 gene. This alteration results from a A to G substitution at nucleotide position 1025, causing the histidine (H) at amino acid position 342 to be replaced by an arginine (R). 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	0.21
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-7.0	.;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	.;D
Vest4		0.68
MutPred		0.86		.;Gain of MoRF binding (P = 0.0307);
MVP		0.86
MPC		1.4
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.83
gMVP		0.82

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: chr1-228582788; COSMIC: COSV52856174; COSMIC: COSV52856174;