1-228394917-C-G

Variant names:

• chr1-228394917-C-G
• NM_145214.3:c.1195G>C

Variant summary

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

The NM_145214.3(TRIM11):​c.1195G>C​(p.Asp399His) 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: -0.394

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19479483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM11	NM_145214.3	c.1195G>C	p.Asp399His	missense_variant	Exon 6 of 6	ENST00000284551.11	NP_660215.1
TRIM11	XM_017002412.3	c.1192G>C	p.Asp398His	missense_variant	Exon 6 of 6		XP_016857901.1
TRIM11	XM_011544285.4	c.964G>C	p.Asp322His	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.1195G>C	p.Asp399His	missense_variant	Exon 6 of 6	1	NM_145214.3	ENSP00000284551.6
TRIM11	ENST00000493030.6	c.820G>C	p.Asp274His	missense_variant	Exon 5 of 5	1		ENSP00000473360.1
TRIM11	ENST00000602582.5	c.589G>C	p.Asp197His	missense_variant	Exon 5 of 5	3		ENSP00000473574.1
ENSG00000270094	ENST00000602963.1	n.159+469C>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1195G>C (p.D399H) alteration is located in exon 6 (coding exon 6) of the TRIM11 gene. This alteration results from a G to C substitution at nucleotide position 1195, causing the aspartic acid (D) at amino acid position 399 to be replaced by a histidine (H). 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	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.42	.;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	.;N
REVEL	Benign	0.14
Sift	Benign	0.048	.;D
Sift4G	Uncertain	0.039	D;T
Polyphen		0.14	.;B
Vest4		0.17
MutPred		0.47		.;Gain of glycosylation at P401 (P = 0.0913);
MVP		0.52
MPC		0.50
ClinPred		0.60	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.052
gMVP		0.50

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: chr1-228582618;