rs116365246

chr4-153295495-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_015271.5(TRIM2):c.969C>T(p.Asn323=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: TRIM2 NM_015271.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0480

Genes affected

TRIM2 (HGNC:15974): (tripartite motif containing 2) 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. The protein localizes to cytoplasmic filaments. It plays a neuroprotective role and functions as an E3-ubiquitin ligase in proteasome-mediated degradation of target proteins. Mutations in this gene can cause early-onset axonal neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 4-153295495-C-T is Benign according to our data. Variant chr4-153295495-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 474618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.048 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM2	NM_015271.5	c.969C>T	p.Asn323=	synonymous_variant	6/12	ENST00000338700.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM2	ENST00000338700.10	c.969C>T	p.Asn323=	synonymous_variant	6/12	1	NM_015271.5

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000207 AC: 52 AN: 251260 Hom.: 0 AF XY: 0.000140 AC XY: 19 AN XY: 135822

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000387

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000113 AC: 165 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.000100 AC XY: 73 AN XY: 727232

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000122

Gnomad4 OTH exome AF: 0.000265

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74454

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000222 Hom.: 0

Bravo AF: 0.000136

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease type 2R Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 02, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	11
Dann	Benign	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

Other links and lift over

dbSNP: rs116365246; hg19: chr4-154216647;