chr5-65609429-T-C

Position:

• chr5-65609429-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_001656.4(TRIM23):​c.858A>G​(p.Ser286Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,614,062 control chromosomes in the GnomAD database, including 219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.010 (14 hom., cov: 32)
  • Exomes 𝑓: 0.016 (205 hom.)
• Consequence: TRIM23 NM_001656.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.118

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 5-65609429-T-C is Benign according to our data. Variant chr5-65609429-T-C is described in ClinVar as [Benign]. Clinvar id is 3033272.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.118 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00997 (1518/152264) while in subpopulation NFE AF= 0.0165 (1122/68016). AF 95% confidence interval is 0.0157. There are 14 homozygotes in gnomad4. There are 674 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM23	NM_001656.4	c.858A>G	p.Ser286Ser	synonymous_variant	6/11	ENST00000231524.14	NP_001647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM23	ENST00000231524.14	c.858A>G	p.Ser286Ser	synonymous_variant	6/11	1	NM_001656.4	ENSP00000231524.9
TRIM23	ENST00000381018.7	c.858A>G	p.Ser286Ser	synonymous_variant	6/13	1		ENSP00000370406.3
TRIM23	ENST00000274327.11	c.858A>G	p.Ser286Ser	synonymous_variant	6/13	1		ENSP00000274327.7
TRIM23	ENST00000508808.1	n.44A>G		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes AF: 0.00998 AC: 1518 AN: 152146 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00278

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.00740

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00820

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.0104 AC: 2622 AN: 251282 Hom.: 19 AF XY: 0.0101 AC XY: 1378 AN XY: 135828

Gnomad AFR exome AF: 0.00326

Gnomad AMR exome AF: 0.00571

Gnomad ASJ exome AF: 0.00357

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00386

Gnomad FIN exome AF: 0.00762

Gnomad NFE exome AF: 0.0175

Gnomad OTH exome AF: 0.00980

GnomAD4 exome AF: 0.0156 AC: 22866 AN: 1461798 Hom.: 205 Cov.: 31 AF XY: 0.0152 AC XY: 11019 AN XY: 727188

Gnomad4 AFR exome AF: 0.00251

Gnomad4 AMR exome AF: 0.00642

Gnomad4 ASJ exome AF: 0.00287

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00424

Gnomad4 FIN exome AF: 0.00886

Gnomad4 NFE exome AF: 0.0187

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.00997 AC: 1518 AN: 152264 Hom.: 14 Cov.: 32 AF XY: 0.00905 AC XY: 674 AN XY: 74454

Gnomad4 AFR AF: 0.00274

Gnomad4 AMR AF: 0.00739

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00820

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.0147 Hom.: 34

Bravo AF: 0.00991

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0171

EpiControl AF: 0.0157

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TRIM23-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.2
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs17240173; hg19: chr5-64905256;