Variant 14-51094698-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001387360.1(TRIM9):c.242A>G(p.Tyr81Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000706 in 1,415,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

TRIM9
NM_001387360.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

Variant links:

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]

TRIM9 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1182147).

BS2

High AC in GnomAdExome at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM9	NM_001387360.1 linkuse as main transcript	c.242A>G	p.Tyr81Cys	missense_variant	1/13	ENST00000684578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM9	ENST00000684578.1 linkuse as main transcript	c.242A>G	p.Tyr81Cys	missense_variant	1/13		NM_001387360.1
TRIM9	ENST00000298355.7 linkuse as main transcript	c.242A>G	p.Tyr81Cys	missense_variant	1/10	1		P1	Q9C026-1
TRIM9	ENST00000360392.4 linkuse as main transcript	c.242A>G	p.Tyr81Cys	missense_variant	1/7	1			Q9C026-5
TRIM9	ENST00000338969.9 linkuse as main transcript	c.242A>G	p.Tyr81Cys	missense_variant	1/12	2			Q9C026-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000381

AC:

AN:

210030

Hom.:

AF XY:

0.0000266

AC XY:

AN XY:

112716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000706

AC:

AN:

1415520

Hom.:

Cov.:

AF XY:

0.00000573

AC XY:

AN XY:

698176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000243

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.242A>G (p.Y81C) alteration is located in exon 1 (coding exon 1) of the TRIM9 gene. This alteration results from a A to G substitution at nucleotide position 242, causing the tyrosine (Y) at amino acid position 81 to be replaced by a cysteine (C). 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

0.31

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.17

Cadd

Pathogenic

Dann

Benign

0.97

DEOGEN2

Benign

0.14

T;.;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.084

T;T;D

Polyphen

0.0010

B;D;D

Vest4

0.34

MutPred

0.29

Loss of phosphorylation at Y81 (P = 0.0423);Loss of phosphorylation at Y81 (P = 0.0423);Loss of phosphorylation at Y81 (P = 0.0423);

MVP

0.19

MPC

1.0

ClinPred

0.19

GERP RS

5.4

Varity_R

0.26

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over