5-65618209-T-C

Position:

• chr5-65618209-T-C

Variant summary

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

The NM_001656.4(TRIM23):​c.128A>G​(p.Asp43Gly) variant causes a missense change involving the alteration of a 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: 7.63

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.128A>G	p.Asp43Gly	missense_variant	2/11	ENST00000231524.14	NP_001647.1
TRIM23	NM_033227.3	c.128A>G	p.Asp43Gly	missense_variant	2/13		NP_150230.1
TRIM23	NM_033228.3	c.128A>G	p.Asp43Gly	missense_variant	2/13		NP_150231.1
TRIM23	XM_017009444.3	c.128A>G	p.Asp43Gly	missense_variant	2/12		XP_016864933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM23	ENST00000231524.14	c.128A>G	p.Asp43Gly	missense_variant	2/11	1	NM_001656.4	ENSP00000231524.9

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

Jan 24, 2023

The c.128A>G (p.D43G) alteration is located in exon 2 (coding exon 2) of the TRIM23 gene. This alteration results from a A to G substitution at nucleotide position 128, causing the aspartic acid (D) at amino acid position 43 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	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Benign	1.3	L;L;L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.0	N;N;N
REVEL	Pathogenic	0.87
Sift	Uncertain	0.028	D;D;D
Sift4G	Uncertain	0.054	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.53
MutPred		0.66		Loss of stability (P = 0.0239);Loss of stability (P = 0.0239);Loss of stability (P = 0.0239);
MVP		0.85
MPC		1.1
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.54
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr5-64914036;