6-30341823-G-A

Variant names:

• chr6-30341823-G-A
• rs766707680
• NM_001369521.2:c.1031G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001369521.2(TRIM39):​c.1031G>A​(p.Arg344Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,612,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: TRIM39 NM_001369521.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02531752).
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369521.2. 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.1031G>A	p.Arg344Lys	missense	Exon 8 of 8	NP_001356450.1	Q9HCM9-2
	TRIM39	NM_021253.4		c.1121G>A	p.Arg374Lys	missense	Exon 9 of 9	NP_067076.2
	TRIM39-RPP21	NM_001199119.1		c.1031G>A	p.Arg344Lys	missense	Exon 6 of 10	NP_001186048.1	A0A096LP39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM39	ENST00000396551.9	TSL:5 MANE Select	c.1031G>A	p.Arg344Lys	missense	Exon 8 of 8	ENSP00000379800.3	Q9HCM9-2
	TRIM39	ENST00000396547.5	TSL:1	c.1121G>A	p.Arg374Lys	missense	Exon 8 of 8	ENSP00000379796.1	Q9HCM9-1
	TRIM39-RPP21	ENST00000623385.3	TSL:5	c.1031G>A	p.Arg344Lys	missense	Exon 7 of 11	ENSP00000485378.1	A0A096LP39

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152076 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000811 AC: 2 AN: 246706 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1460776 Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18 AN XY: 726706

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152076 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74260

African (AFR) AF: 0.00 AC: 0 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000142 Hom.: 0

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.00000842 AC: 1

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	0.087
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.0
PROVEAN	Benign	0.91	N
REVEL	Benign	0.063
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.076
MutPred		0.51		Gain of methylation at R374 (P = 0.0041)
MVP		0.18
MPC		1.5
ClinPred		0.049	T
GERP RS		3.0
Varity_R		0.056
gMVP		0.69
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs766707680; hg19: chr6-30309600;