rs36133

Variant names:

• chr5-65596688-G-A
• rs36133
• NM_001656.4:c.1310-157C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001656.4(TRIM23):​c.1310-157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 151,834 control chromosomes in the GnomAD database, including 34,499 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34499 hom., cov: 30)
• Consequence: TRIM23 NM_001656.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM23	NM_001656.4	c.1310-157C>T		intron_variant	Intron 8 of 10	ENST00000231524.14	NP_001647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM23	ENST00000231524.14	c.1310-157C>T		intron_variant	Intron 8 of 10	1	NM_001656.4	ENSP00000231524.9
TRIM23	ENST00000381018.7	c.1310-157C>T		intron_variant	Intron 8 of 12	1		ENSP00000370406.3
TRIM23	ENST00000274327.11	c.1310-157C>T		intron_variant	Intron 8 of 12	1		ENSP00000274327.7

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101258 AN: 151716 Hom.: 34461 Cov.: 30

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.636

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.667 AC: 101346 AN: 151834 Hom.: 34499 Cov.: 30 AF XY: 0.662 AC XY: 49104 AN XY: 74214

African (AFR) AF: 0.787 AC: 32591 AN: 41392

American (AMR) AF: 0.557 AC: 8497 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2077 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2207 AN: 5146

South Asian (SAS) AF: 0.650 AC: 3123 AN: 4802

European-Finnish (FIN) AF: 0.638 AC: 6714 AN: 10530

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44014 AN: 67928

Other (OTH) AF: 0.632 AC: 1329 AN: 2102

Alfa AF: 0.657 Hom.: 18661

Bravo AF: 0.665

Asia WGS AF: 0.570 AC: 1984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.44
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs36133; hg19: chr5-64892515;