3-138161973-ATG-GTA

Variant names:

• chr3-138161973-ATG-GTA
• NM_016216.4:c.1549_1551delCATinsTAC
• DBR1 p.His517Tyr

Variant summary

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

The NM_016216.4(DBR1):​c.1549_1551delCATinsTAC​(p.His517Tyr) variant causes a missense 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 Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DBR1 NM_016216.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 0 publications found

Genes affected

DBR1 (HGNC:15594): (debranching RNA lariats 1) The protein encoded by this gene is an RNA lariat debranching enzyme that hydrolyzes 2'-5' prime branched phosphodiester bonds. The encoded protein specifically targets the bonds at the branch point of excised lariat intron RNA, converting them to linear molecules that are then degraded. This protein may also be involved in retroviral replication. [provided by RefSeq, Nov 2011]

DBR1 Gene-Disease associations (from GenCC):

• encephalitis, acute, infection (viral)-induced, susceptibility to, 11

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• xerosis and growth failure with immune and pulmonary dysfunction syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016216.4. 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
	DBR1	NM_016216.4	MANE Select	c.1549_1551delCATinsTAC	p.His517Tyr	missense	N/A	NP_057300.2	Q9UK59-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBR1	ENST00000260803.9	TSL:1 MANE Select	c.1549_1551delCATinsTAC	p.His517Tyr	missense	N/A	ENSP00000260803.4	Q9UK59-1
	DBR1	ENST00000698924.1		c.1468_1470delCATinsTAC	p.His490Tyr	missense	N/A	ENSP00000514035.1	A0A8V8TNX0
	DBR1	ENST00000698922.1		c.1324_1326delCATinsTAC	p.His442Tyr	missense	N/A	ENSP00000514033.1	A0A8V8TMF7

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		1.5

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: chr3-137880815;