5-181195516-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_203293.3(TRIM7):​c.1186C>T​(p.Arg396Trp) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

TRIM7
NM_203293.3 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0620
Variant links:
Genes affected
TRIM7 (HGNC:16278): (tripartite motif containing 7) 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, a B-box type 2, and a coiled-coil region. The protein localizes to both the nucleus and the cytoplasm, and may represent a participant in the initiation of glycogen synthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
TRIM7-AS1 (HGNC:40764): (TRIM7 antisense RNA 1)
TRIM7-AS2 (HGNC:56031): (TRIM7 antisense RNA 2)

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.976

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM7NM_203293.3 linkc.1186C>T p.Arg396Trp missense_variant Exon 7 of 7 ENST00000274773.12 NP_976038.1 Q9C029-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM7ENST00000274773.12 linkc.1186C>T p.Arg396Trp missense_variant Exon 7 of 7 1 NM_203293.3 ENSP00000274773.7 Q9C029-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000302

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1186C>T (p.R396W) alteration is located in exon 7 (coding exon 7) of the TRIM7 gene. This alteration results from a C to T substitution at nucleotide position 1186, causing the arginine (R) at amino acid position 396 to be replaced by a tryptophan (W). 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
0.22
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T;.;.;.
Eigen
Uncertain
0.19
Eigen_PC
Benign
-0.068
FATHMM_MKL
Benign
0.34
N
LIST_S2
Uncertain
0.97
D;D;D;.
M_CAP
Uncertain
0.23
D
MetaRNN
Pathogenic
0.98
D;D;D;D
MetaSVM
Uncertain
0.027
D
MutationAssessor
Pathogenic
4.0
H;.;.;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-6.5
D;D;D;D
REVEL
Uncertain
0.52
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
1.0
D;.;D;.
Vest4
0.80
MutPred
0.90
Loss of disorder (P = 0.0373);.;.;.;
MVP
0.82
MPC
1.7
ClinPred
1.0
D
GERP RS
1.7
Varity_R
0.60
gMVP
0.88

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.

Other links and lift over

dbSNP: rs991138763; hg19: chr5-180622516; COSMIC: COSV51243722; COSMIC: COSV51243722; API