14-50998094-C-A

Position:

• chr14-50998094-C-A

Variant summary

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

The NM_001387360.1(TRIM9):​c.1559G>T​(p.Gly520Val) variant causes a missense change involving the alteration of a 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: 32)
• Consequence: TRIM9 NM_001387360.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82

Genes affected

TRIM9 (HGNC:16288): (tripartite motif containing 9) 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. The protein localizes to cytoplasmic bodies. Its function has not been identified. Alternate splicing of this gene generates two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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, 0.93

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM9	NM_001387360.1	c.1559G>T	p.Gly520Val	missense_variant	7/13	ENST00000684578.1	NP_001374289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM9	ENST00000684578.1	c.1559G>T	p.Gly520Val	missense_variant	7/13		NM_001387360.1	ENSP00000507131.1
TRIM9	ENST00000298355.7	c.1559G>T	p.Gly520Val	missense_variant	7/10	1		ENSP00000298355.3
TRIM9	ENST00000360392.4	c.1559G>T	p.Gly520Val	missense_variant	7/7	1		ENSP00000353561.4
TRIM9	ENST00000338969.9	c.1547G>T	p.Gly516Val	missense_variant	7/12	2		ENSP00000342970.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jan 20, 2023

The c.1559G>T (p.G520V) alteration is located in exon 7 (coding exon 7) of the TRIM9 gene. This alteration results from a G to T substitution at nucleotide position 1559, causing the glycine (G) at amino acid position 520 to be replaced by a valine (V). 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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.;.
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Uncertain	0.018	D
MutationAssessor	Uncertain	2.6	M;.;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-8.0	D;D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.95	P;D;D
Vest4		0.92
MutPred		0.78		Loss of disorder (P = 0.046);.;Loss of disorder (P = 0.046);
MVP		0.71
MPC		2.1
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.89
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: chr14-51464812;