1-212064996-G-C

Position:

• chr1-212064996-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016448.4(DTL):​c.606G>C​(p.Lys202Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DTL NM_016448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87

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]

DTL (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36781627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTL	NM_016448.4	c.606G>C	p.Lys202Asn	missense_variant	7/15	ENST00000366991.5	NP_057532.4
DTL	NM_001286230.2	c.480G>C	p.Lys160Asn	missense_variant	6/14		NP_001273159.2
DTL	XM_011509614.2	c.420G>C	p.Lys140Asn	missense_variant	7/15		XP_011507916.1
DTL	NM_001286229.2	c.-104G>C		5_prime_UTR_variant	6/13		NP_001273158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTL	ENST00000366991.5	c.606G>C	p.Lys202Asn	missense_variant	7/15	1	NM_016448.4	ENSP00000355958.4
DTL	ENST00000542077.5	c.480G>C	p.Lys160Asn	missense_variant	6/14	2		ENSP00000443870.1
DTL	ENST00000475419.5	n.525G>C		non_coding_transcript_exon_variant	6/13	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2022

The c.606G>C (p.K202N) alteration is located in exon 7 (coding exon 7) of the DTL gene. This alteration results from a G to C substitution at nucleotide position 606, causing the lysine (K) at amino acid position 202 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	.;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.051	T;T
Polyphen		1.0	D;D
Vest4		0.61
MutPred		0.40		.;Loss of methylation at K202 (P = 0.0101);
MVP		0.80
MPC		0.62
ClinPred		0.97	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.49
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-212238338;