chr3-38110169-C-T

Variant names:

Variant summary

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

The NM_007335.4(DLEC1):c.3331C>T(p.Arg1111Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,614,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

DLEC1
NM_007335.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.39

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 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=0.014303654).

BP6

Variant 3-38110169-C-T is Benign according to our data. Variant chr3-38110169-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653666.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLEC1	NM_007335.4 link	c.3331C>T	p.Arg1111Cys	missense_variant	Exon 23 of 37	ENST00000308059.11	NP_031361.2	Q9Y238-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLEC1	ENST00000308059.11 link	c.3331C>T	p.Arg1111Cys	missense_variant	Exon 23 of 37	1	NM_007335.4	ENSP00000308597.6	Q9Y238-1
DLEC1	ENST00000346219.7 link	c.3331C>T	p.Arg1111Cys	missense_variant	Exon 23 of 36	1		ENSP00000315914.5	Q9Y238-3
DLEC1	ENST00000477260.1 link	n.360C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3
ACAA1	ENST00000451419.1 link	n.300-6376G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000100

AC:

AN:

249554

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.000452

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000269

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000265

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.000725

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DLEC1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.013

Sift

Benign

0.084

T;T

Sift4G

Uncertain

0.054

T;T

Polyphen

0.0080

B;B

Vest4

0.18

MVP

0.30

MPC

0.14

ClinPred

0.019

GERP RS

-2.6

Varity_R

0.077

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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