Genetic Variant DLEC1:p.Arg139Gln (chr3-38045547-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007335.4(DLEC1):c.416G>A(p.Arg139Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000844 in 1,611,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

DLEC1
NM_007335.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.115130216).

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.416G>A	p.Arg139Gln	missense	Exon 2 of 37	NP_031361.2	Q9Y238-1
DLEC1	NM_007337.4		c.416G>A	p.Arg139Gln	missense	Exon 2 of 36	NP_031363.2	Q9Y238-3
DLEC1	NM_001321153.2		c.416G>A	p.Arg139Gln	missense	Exon 2 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.416G>A	p.Arg139Gln	missense	Exon 2 of 37	ENSP00000308597.6	Q9Y238-1
DLEC1	ENST00000346219.7	TSL:1	c.416G>A	p.Arg139Gln	missense	Exon 2 of 36	ENSP00000315914.5	Q9Y238-3
DLEC1	ENST00000896006.1		c.416G>A	p.Arg139Gln	missense	Exon 2 of 37	ENSP00000566065.1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000138

AC:

AN:

246648

AF XY:

0.000127

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000472

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000393

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000714

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.0000843

AC:

123

AN:

1459826

Hom.:

Cov.:

AF XY:

0.0000826

AC XY:

AN XY:

726254

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33324

American (AMR)

AF:

0.000429

AC:

AN:

44242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25990

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39616

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000792

AC:

AN:

1111264

Other (OTH)

AF:

0.000182

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41400

American (AMR)

AF:

0.000524

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68022

Other (OTH)

AF:

0.000958

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000243

AC:

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0087

Eigen

Benign

0.072

Eigen_PC

Benign

0.092

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.77

M_CAP

Benign

0.0059

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

PhyloP100

2.9

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.32

REVEL

Benign

0.057

Sift

Benign

0.30

Sift4G

Benign

0.16

Polyphen

0.92

Vest4

0.54

MVP

0.29

MPC

0.14

ClinPred

0.045

GERP RS

4.7

Varity_R

0.088

gMVP

0.13

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over