1-212080704-G-C

Variant names:

• chr1-212080704-G-C
• NM_016448.4:c.1215G>C
• DTL p.Thr405Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016448.4(DTL):​c.1215G>C​(p.Thr405Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T405T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DTL NM_016448.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 0 publications found

Genes affected

DTL (HGNC:30288): (denticleless E3 ubiquitin protein ligase homolog) Contributes to ubiquitin-protein transferase activity. Involved in several processes, including protein ubiquitination; regulation of G2/M transition of mitotic cell cycle; and translesion synthesis. Located in centrosome; cytosol; and nuclear lumen. Part of Cul4A-RING E3 ubiquitin ligase complex and Cul4B-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-0.005 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016448.4. 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
	DTL	NM_016448.4	MANE Select	c.1215G>C	p.Thr405Thr	synonymous	Exon 13 of 15	NP_057532.4	Q9NZJ0-1
	DTL	NM_001286230.2		c.1089G>C	p.Thr363Thr	synonymous	Exon 12 of 14	NP_001273159.2	F5GZ90
	DTL	NM_001286229.2		c.402G>C	p.Thr134Thr	synonymous	Exon 11 of 13	NP_001273158.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTL	ENST00000366991.5	TSL:1 MANE Select	c.1215G>C	p.Thr405Thr	synonymous	Exon 13 of 15	ENSP00000355958.4	Q9NZJ0-1
	DTL	ENST00000935628.1		c.1263G>C	p.Thr421Thr	synonymous	Exon 14 of 16	ENSP00000605687.1
	DTL	ENST00000935625.1		c.1212G>C	p.Thr404Thr	synonymous	Exon 13 of 15	ENSP00000605684.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.5
DANN	Benign	0.61
PhyloP100		-0.0050
Mutation Taster		=97/3	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

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

Other links and lift over

hg19: chr1-212254046;