5-65611875-T-A

Position:

• chr5-65611875-T-A

Variant summary

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

The NM_001656.4(TRIM23):​c.373A>T​(p.Ile125Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM23 NM_001656.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14

Genes affected

TRIM23 (HGNC:660): (tripartite motif containing 23) 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. This protein is also a member of the ADP ribosylation factor family of guanine nucleotide-binding family of proteins. Its carboxy terminus contains an ADP-ribosylation factor domain and a guanine nucleotide binding site, while the amino terminus contains a GTPase activating protein domain which acts on the guanine nucleotide binding site. The protein localizes to lysosomes and the Golgi apparatus. It plays a role in the formation of intracellular transport vesicles, their movement from one compartment to another, and phopholipase D activation. Three alternatively spliced transcript variants for this gene have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM23	NM_001656.4	c.373A>T	p.Ile125Phe	missense_variant	4/11	ENST00000231524.14	NP_001647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM23	ENST00000231524.14	c.373A>T	p.Ile125Phe	missense_variant	4/11	1	NM_001656.4	ENSP00000231524.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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 06, 2022

The c.373A>T (p.I125F) alteration is located in exon 4 (coding exon 4) of the TRIM23 gene. This alteration results from a A to T substitution at nucleotide position 373, causing the isoleucine (I) at amino acid position 125 to be replaced by a phenylalanine (F). 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	0.37
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	0.089
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.077
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.15	B;B;B
Vest4		0.71
MutPred		0.45		Loss of catalytic residue at I125 (P = 0.0681);Loss of catalytic residue at I125 (P = 0.0681);Loss of catalytic residue at I125 (P = 0.0681);
MVP		0.36
MPC		1.6
ClinPred		0.80	D
GERP RS		4.1
Varity_R		0.21
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-64907702;