rs775272809

Variant names:

• chr6-30340279-C-G
• rs775272809
• ENST00000396547.5:c.811C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-30340279-C-G
• chr6-30340279-C-T

Variant summary

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

The NM_021253.4(TRIM39):​c.811C>G​(p.Pro271Ala) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P271S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM39 NM_021253.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.839
• Publications: 2 publications found

Genes affected

TRIM39 (HGNC:10065): (tripartite motif containing 39) 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 function of this protein has not been identified. This gene lies within the major histocompatibility complex class I region on chromosome 6. Alternate splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

TRIM39-RPP21 (HGNC:38845): (TRIM39-RPP21 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TRIM39 (tripartite motif-containing 39) and RPP21 (ribonuclease P/MRP 21kDa subunit) genes on chromosome 6. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055951297).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021253.4. 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
	TRIM39	NM_001369521.2	MANE Select	c.804-226C>G		intron	N/A	NP_001356450.1	Q9HCM9-2
	TRIM39	NM_021253.4		c.811C>G	p.Pro271Ala	missense	Exon 7 of 9	NP_067076.2
	TRIM39-RPP21	NM_001199119.1		c.804-226C>G		intron	N/A	NP_001186048.1	A0A096LP39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM39	ENST00000396547.5	TSL:1	c.811C>G	p.Pro271Ala	missense	Exon 6 of 8	ENSP00000379796.1	Q9HCM9-1
	TRIM39	ENST00000396551.9	TSL:5 MANE Select	c.804-226C>G		intron	N/A	ENSP00000379800.3	Q9HCM9-2
	TRIM39-RPP21	ENST00000623385.3	TSL:5	c.804-226C>G		intron	N/A	ENSP00000485378.1	A0A096LP39

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.083
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.3
DANN	Benign	0.47
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.78	N
PhyloP100		-0.84
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.031
Sift	Benign	0.66	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.37		Loss of stability (P = 0.0303)
MVP		0.31
MPC		0.46
ClinPred		0.031	T
GERP RS		-1.5
Varity_R		0.022
gMVP		0.068
Mutation Taster		=96/4	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: rs775272809; hg19: chr6-30308056;