3-138162038-T-C

Variant names:

• chr3-138162038-T-C
• NM_016216.4:c.1486A>G

Variant summary

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

The NM_016216.4(DBR1):​c.1486A>G​(p.Thr496Ala) 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: DBR1 NM_016216.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.246
• 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: 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=0.04458484).
• BP6: Variant 3-138162038-T-C is Benign according to our data. Variant chr3-138162038-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2327165.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1486A>G	p.Thr496Ala	missense	Exon 8 of 8	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.1486A>G	p.Thr496Ala	missense	Exon 8 of 8	ENSP00000260803.4	Q9UK59-1
	DBR1	ENST00000698924.1		c.1405A>G	p.Thr469Ala	missense	Exon 7 of 7	ENSP00000514035.1	A0A8V8TNX0
	DBR1	ENST00000698922.1		c.1261A>G	p.Thr421Ala	missense	Exon 7 of 7	ENSP00000514033.1	A0A8V8TMF7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.074
DANN	Benign	0.29
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.035	N
PhyloP100		-0.25
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.0060
Sift	Benign	0.58	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.020
MutPred		0.12		Loss of glycosylation at T496 (P = 0.009)
MVP		0.13
MPC		0.24
ClinPred		0.0071	T
GERP RS		-5.1
Varity_R		0.017
gMVP		0.046
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

hg19: chr3-137880880; COSMIC: COSV106055706; COSMIC: COSV106055706;