chr11-5665384-C-A

Variant names:

• chr11-5665384-C-A
• rs1338700202
• NM_033034.3:c.907G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_033034.3(TRIM5):​c.907G>T​(p.Val303Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM5 NM_033034.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.513
• Publications: 0 publications found

Genes affected

TRIM5 (HGNC:16276): (tripartite motif containing 5) 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 forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

ENSG00000239920 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035969168).
• BP6: Variant 11-5665384-C-A is Benign according to our data. Variant chr11-5665384-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2619963.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033034.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM5	NM_033034.3	MANE Select	c.907G>T	p.Val303Leu	missense	Exon 8 of 8	NP_149023.2	Q9C035-1
	TRIM5	NM_033092.4		c.*123G>T		3_prime_UTR	Exon 7 of 7	NP_149083.2	Q9C035-3
	TRIM5	NM_001410958.1		c.*8G>T		3_prime_UTR	Exon 7 of 7	NP_001397887.1	A0A804HHS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM5	ENST00000380034.8	TSL:2 MANE Select	c.907G>T	p.Val303Leu	missense	Exon 8 of 8	ENSP00000369373.3	Q9C035-1
	TRIM5	ENST00000396847.7	TSL:1	c.*123G>T		3_prime_UTR	Exon 7 of 7	ENSP00000380058.3	Q9C035-3
	ENSG00000239920	ENST00000380259.7	TSL:5	n.231+12820G>T		intron	N/A	ENSP00000369609.3	A0A2U3TZJ3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.018
DANN	Benign	0.12
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-3.1	N
PhyloP100		-0.51
PrimateAI	Benign	0.26	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.051
MutPred		0.65		Loss of catalytic residue at V303 (P = 0.0751)
MVP		0.17
MPC		0.051
ClinPred		0.051	T
GERP RS		-1.9
Varity_R		0.026
gMVP		0.060
Mutation Taster		=98/2	polymorphism

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: rs1338700202; hg19: chr11-5686614;