5-181195354-G-C

Position:

• chr5-181195354-G-C

Variant summary

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

The NM_203293.3(TRIM7):​c.1348C>G​(p.Arg450Gly) 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. 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)
• Consequence: TRIM7 NM_203293.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.309

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-AS2 (HGNC:56031): (TRIM7 antisense RNA 2)

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=0.18618599).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM7	NM_203293.3	c.1348C>G	p.Arg450Gly	missense_variant	7/7	ENST00000274773.12	NP_976038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM7	ENST00000274773.12	c.1348C>G	p.Arg450Gly	missense_variant	7/7	1	NM_203293.3	ENSP00000274773.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Apr 20, 2024

The c.1348C>G (p.R450G) alteration is located in exon 7 (coding exon 7) of the TRIM7 gene. This alteration results from a C to G substitution at nucleotide position 1348, causing the arginine (R) at amino acid position 450 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	Uncertain	0.38
BayesDel_addAF	Benign	0.0060	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T;.;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.078	N
LIST_S2	Uncertain	0.87	D;D;D;.
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.2	L;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Uncertain	0.39
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	0.32	T;T;T;T
Polyphen		1.0	D;.;D;.
Vest4		0.32
MutPred		0.58		Gain of glycosylation at S451 (P = 0.0688);.;.;.;
MVP		0.67
MPC		1.9
ClinPred		0.38	T
GERP RS		0.70
Varity_R		0.11
gMVP		0.69

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: chr5-180622354;