Variant 5-65618146-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001656.4(TRIM23):c.191C>T(p.Pro64Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TRIM23
NM_001656.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.54

Variant links:

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]

TRIM23 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.191C>T	p.Pro64Leu	missense_variant	2/11	ENST00000231524.14	NP_001647.1	P36406-1
TRIM23	NM_033227.3 linkuse as main transcript	c.191C>T	p.Pro64Leu	missense_variant	2/13		NP_150230.1	P36406-2
TRIM23	NM_033228.3 linkuse as main transcript	c.191C>T	p.Pro64Leu	missense_variant	2/13		NP_150231.1	P36406-3
TRIM23	XM_017009444.3 linkuse as main transcript	c.191C>T	p.Pro64Leu	missense_variant	2/12		XP_016864933.1	P36406-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM23	ENST00000231524.14 linkuse as main transcript	c.191C>T	p.Pro64Leu	missense_variant	2/11	1	NM_001656.4	ENSP00000231524.9		P36406-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251268

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.191C>T (p.P64L) alteration is located in exon 2 (coding exon 2) of the TRIM23 gene. This alteration results from a C to T substitution at nucleotide position 191, causing the proline (P) at amino acid position 64 to be replaced by a leucine (L). 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

0.71

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;.;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Benign

-0.61

MutationAssessor

Benign

-0.75

N;N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-2.0

N;N;N

REVEL

Uncertain

0.47

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

0.68

P;P;P

Vest4

0.67

MutPred

0.76

Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);

MVP

0.70

MPC

0.62

ClinPred

0.70

GERP RS

5.4

Varity_R

0.45

gMVP

0.67

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over