5-181195342-T-G

Position:

• chr5-181195342-T-G

Variant summary

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

The NM_203293.3(TRIM7):​c.1360A>C​(p.Ser454Arg) 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. 14/21 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: 0.374

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:):

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=0.16842172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM7	NM_203293.3	c.1360A>C	p.Ser454Arg	missense_variant	7/7	ENST00000274773.12	NP_976038.1
TRIM7-AS2	NR_183283.1	n.1538T>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM7	ENST00000274773.12	c.1360A>C	p.Ser454Arg	missense_variant	7/7	1	NM_203293.3	ENSP00000274773	P1

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

Sep 20, 2023

The c.1360A>C (p.S454R) alteration is located in exon 7 (coding exon 7) of the TRIM7 gene. This alteration results from a A to C substitution at nucleotide position 1360, causing the serine (S) at amino acid position 454 to be replaced by an arginine (R). 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	0.21
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0081	T;.;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.62	T;T;T;.
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.4	L;.;.;.
MutationTaster	Benign	0.98	N;N;N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.37	T;T;T;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.63	P;.;P;.
Vest4		0.075
MutPred		0.48		Loss of disorder (P = 0.0911);.;.;.;
MVP		0.76
MPC		1.3
ClinPred		0.62	D
GERP RS		4.8
Varity_R		0.23
gMVP		0.65

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: chr5-180622342;