1-228400998-C-T

Variant names:

• chr1-228400998-C-T
• rs770229664
• NM_145214.3:c.701G>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.701G>A​(p.Gly234Asp) 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. 14/21 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)
• Consequence: TRIM11 NM_145214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0740

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=0.04637167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM11	NM_145214.3	c.701G>A	p.Gly234Asp	missense_variant	Exon 3 of 6	ENST00000284551.11	NP_660215.1
TRIM11	XM_017002412.3	c.698G>A	p.Gly233Asp	missense_variant	Exon 3 of 6		XP_016857901.1
TRIM11	XM_011544285.4	c.504+1068G>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.701G>A	p.Gly234Asp	missense_variant	Exon 3 of 6	1	NM_145214.3	ENSP00000284551.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.701G>A (p.G234D) 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 701, causing the glycine (G) at amino acid position 234 to be replaced by an aspartic acid (D). 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	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.49
DEOGEN2	Benign	0.0066	T;T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	.;L;L
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.44	.;N;N
REVEL	Benign	0.028
Sift	Benign	0.79	.;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		0.0, 0.012	.;B;B
Vest4		0.25
MutPred		0.31		.;Gain of disorder (P = 0.122);Gain of disorder (P = 0.122);
MVP		0.19
MPC		0.52
ClinPred		0.023	T
GERP RS		-0.098
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.53

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: rs770229664; hg19: chr1-228588699;