14-51009085-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001387360.1(TRIM9):c.1301T>G(p.Val434Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: TRIM9 NM_001387360.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26024812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM9	NM_001387360.1	c.1301T>G	p.Val434Gly	missense_variant	5/13	ENST00000684578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM9	ENST00000684578.1	c.1301T>G	p.Val434Gly	missense_variant	5/13		NM_001387360.1
TRIM9	ENST00000298355.7	c.1301T>G	p.Val434Gly	missense_variant	5/10	1		P1
TRIM9	ENST00000360392.4	c.1301T>G	p.Val434Gly	missense_variant	5/7	1
TRIM9	ENST00000338969.9	c.1301T>G	p.Val434Gly	missense_variant	5/12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461556 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.00

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

Nov 07, 2023

The c.1301T>G (p.V434G) alteration is located in exon 5 (coding exon 5) of the TRIM9 gene. This alteration results from a T to G substitution at nucleotide position 1301, causing the valine (V) at amino acid position 434 to be replaced by a glycine (G). 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	0.093
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.0080	B;B;B
Vest4		0.43
MutPred		0.68		Loss of stability (P = 0.0143);Loss of stability (P = 0.0143);Loss of stability (P = 0.0143);
MVP		0.35
MPC		1.1
ClinPred		0.90	D
GERP RS		5.9
Varity_R		0.53
gMVP		0.68

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: chr14-51475803;