Genetic Variant DLEC1:p.Glu1214Gln (chr3-38112335-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_007335.4(DLEC1):c.3640G>C(p.Glu1214Gln) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1214K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

DLEC1
NM_007335.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.40

Publications

1 publications found

Variant links:

Genes affected

DLEC1 (HGNC:2899): (DLEC1 cilia and flagella associated protein) The cytogenetic location of this gene is 3p21.3, and it is located in a region that is commonly deleted in a variety of malignancies. Down-regulation of this gene has been observed in several human cancers including lung, esophageal, renal tumors, and head and neck squamous cell carcinoma. In some cases, reduced expression of this gene in tumor cells is a result of aberrant promoter methylation. Several alternatively spliced transcripts have been observed that contain disrupted coding regions and likely encode nonfunctional proteins.[provided by RefSeq, Mar 2016]

DLEC1 links:

ACAA1 (HGNC:82): (acetyl-CoA acyltransferase 1) This gene encodes an enzyme operative in the beta-oxidation system of the peroxisomes. Deficiency of this enzyme leads to pseudo-Zellweger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACAA1 links:

LOC105377033 (HGNC:):

LOC105377033 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31627572).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007335.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLEC1	NM_007335.4	MANE Select	c.3640G>C	p.Glu1214Gln	missense	Exon 25 of 37	NP_031361.2	Q9Y238-1
DLEC1	NM_007337.4		c.3640G>C	p.Glu1214Gln	missense	Exon 25 of 36	NP_031363.2	Q9Y238-3
DLEC1	NM_001321153.2		c.3649G>C	p.Glu1217Gln	missense	Exon 25 of 37	NP_001308082.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLEC1	ENST00000308059.11	TSL:1 MANE Select	c.3640G>C	p.Glu1214Gln	missense	Exon 25 of 37	ENSP00000308597.6	Q9Y238-1
DLEC1	ENST00000346219.7	TSL:1	c.3640G>C	p.Glu1214Gln	missense	Exon 25 of 36	ENSP00000315914.5	Q9Y238-3
DLEC1	ENST00000896006.1		c.3649G>C	p.Glu1217Gln	missense	Exon 25 of 37	ENSP00000566065.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0087

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

3.4

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

REVEL

Benign

0.065

Sift

Benign

0.099

Sift4G

Benign

0.061

Polyphen

0.54

Vest4

0.53

MVP

0.32

MPC

0.28

ClinPred

0.93

GERP RS

3.8

Varity_R

0.13

gMVP

0.43

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over