1-212044752-T-G

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016448.4(DTL):c.271T>G(p.Phe91Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,606,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DTL
NM_016448.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.79

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051446408).

BP6

Variant 1-212044752-T-G is Benign according to our data. Variant chr1-212044752-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3086072.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTL	NM_016448.4 link	c.271T>G	p.Phe91Val	missense_variant	Exon 3 of 15	ENST00000366991.5	NP_057532.4	Q9NZJ0-1
DTL	NM_001286230.2 link	c.145T>G	p.Phe49Val	missense_variant	Exon 2 of 14		NP_001273159.2	B4E0E6
DTL	XM_011509614.2 link	c.85T>G	p.Phe29Val	missense_variant	Exon 3 of 15		XP_011507916.1
DTL	NM_001286229.2 link	c.-439T>G		5_prime_UTR_variant	Exon 2 of 13		NP_001273158.2	Q9NZJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DTL	ENST00000366991.5 link	c.271T>G	p.Phe91Val	missense_variant	Exon 3 of 15	1	NM_016448.4	ENSP00000355958.4	Q9NZJ0-1
DTL	ENST00000542077.5 link	c.145T>G	p.Phe49Val	missense_variant	Exon 2 of 14	2		ENSP00000443870.1	F5GZ90
DTL	ENST00000475419.5 link	n.190T>G		non_coding_transcript_exon_variant	Exon 2 of 13	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454374

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 19, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.050

.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.28

.;N

PrimateAI

Benign

0.39

PROVEAN

Benign

0.070

N;N

REVEL

Benign

0.061

Sift

Benign

0.50

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0

B;B

Vest4

0.17

MutPred

0.40

.;Gain of catalytic residue at F91 (P = 0.0516);

MVP

0.53

MPC

0.41

ClinPred

0.20

GERP RS

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.31

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over