6-30340273-AAT-CAC

Variant names:

• chr6-30340273-AAT-CAC
• ENST00000396547.5:c.805_807delAATinsCAC
• TRIM39 p.Asn269His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_021253.4(TRIM39):​c.805_807delAATinsCAC​(p.Asn269His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM39 NM_021253.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.804-232_804-230delAATinsCAC		intron	N/A	NP_001356450.1	Q9HCM9-2
	TRIM39	NM_021253.4		c.805_807delAATinsCAC	p.Asn269His	missense splice_region	N/A	NP_067076.2
	TRIM39-RPP21	NM_001199119.1		c.804-232_804-230delAATinsCAC		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.805_807delAATinsCAC	p.Asn269His	missense splice_region	N/A	ENSP00000379796.1	Q9HCM9-1
	TRIM39	ENST00000396551.9	TSL:5 MANE Select	c.804-232_804-230delAATinsCAC		intron	N/A	ENSP00000379800.3	Q9HCM9-2
	TRIM39-RPP21	ENST00000623385.3	TSL:5	c.804-232_804-230delAATinsCAC		intron	N/A	ENSP00000485378.1	A0A096LP39

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.031

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-30308050;