Genetic Variant NM_007335.4:c.250C>T (chr3-38039475-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_007335.4(DLEC1):c.250C>T(p.Pro84Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,613,932 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 2 hom., cov: 34)

Exomes 𝑓: 0.00045 ( 8 hom. )

Consequence

DLEC1
NM_007335.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.27

Publications

6 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060677826).

BP6

Variant 3-38039475-C-T is Benign according to our data. Variant chr3-38039475-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2653661.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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.250C>T	p.Pro84Ser	missense	Exon 1 of 37	NP_031361.2	Q9Y238-1
DLEC1	NM_007337.4		c.250C>T	p.Pro84Ser	missense	Exon 1 of 36	NP_031363.2	Q9Y238-3
DLEC1	NM_001321153.2		c.250C>T	p.Pro84Ser	missense	Exon 1 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.250C>T	p.Pro84Ser	missense	Exon 1 of 37	ENSP00000308597.6	Q9Y238-1
DLEC1	ENST00000346219.7	TSL:1	c.250C>T	p.Pro84Ser	missense	Exon 1 of 36	ENSP00000315914.5	Q9Y238-3
DLEC1	ENST00000896006.1		c.250C>T	p.Pro84Ser	missense	Exon 1 of 37	ENSP00000566065.1

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152286

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000872

AC:

217

AN:

248836

AF XY:

0.000821

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000449

AC:

657

AN:

1461646

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

329

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33474

American (AMR)

AF:

0.000335

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0171

AC:

447

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000998

AC:

111

AN:

1111846

Other (OTH)

AF:

0.00129

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

134

178

223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000453

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41482

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68046

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000883

Hom.:

Bravo

AF:

0.000570

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00108

AC:

ExAC

AF:

0.000653

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.81

M_CAP

Benign

0.029

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.5

PhyloP100

2.3

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.20

Sift

Benign

0.044

Sift4G

Benign

0.11

Polyphen

0.98

Vest4

0.39

MVP

0.66

MPC

0.53

ClinPred

0.17

GERP RS

4.6

PromoterAI

0.067

Neutral

(source)

Varity_R

0.41

gMVP

0.44

Mutation Taster

=99/1

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

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