3-38059754-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007335.4(DLEC1):c.575C>T(p.Ser192Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,613,884 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.013 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 34 hom. )

Consequence

DLEC1
NM_007335.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.63

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045306385).

BP6

Variant 3-38059754-C-T is Benign according to our data. Variant chr3-38059754-C-T is described in ClinVar as [Benign]. Clinvar id is 769271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0129 (1961/152244) while in subpopulation AFR AF = 0.0432 (1793/41540). AF 95% confidence interval is 0.0415. There are 38 homozygotes in GnomAd4. There are 923 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLEC1	NM_007335.4 link	c.575C>T	p.Ser192Phe	missense_variant	Exon 3 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.575C>T	p.Ser192Phe	missense_variant	Exon 3 of 37	1	NM_007335.4	ENSP00000308597.6	Q9Y238-1
DLEC1	ENST00000346219.7 link	c.575C>T	p.Ser192Phe	missense_variant	Exon 3 of 36	1		ENSP00000315914.5	Q9Y238-3
DLEC1	ENST00000440294.6 link	n.596C>T		non_coding_transcript_exon_variant	Exon 3 of 17	2

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1954

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00320

AC:

798

AN:

249274

AF XY:

0.00229

show subpopulations

Gnomad AFR exome

AF:

0.0419

Gnomad AMR exome

AF:

0.00293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00150

AC:

2197

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

986

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0439

AC:

1469

AN:

33470

Gnomad4 AMR exome

AF:

0.00347

AC:

155

AN:

44682

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26132

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39694

Gnomad4 SAS exome

AF:

0.000162

AC:

AN:

86236

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53418

Gnomad4 NFE exome

AF:

0.000262

AC:

291

AN:

1111858

Gnomad4 Remaining exome

AF:

0.00402

AC:

243

AN:

60382

Heterozygous variant carriers

198

298

397

496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.0129

AC:

1961

AN:

152244

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

923

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0432

AC:

0.0431632

AN:

0.0431632

Gnomad4 AMR

AF:

0.00660

AC:

0.00660303

AN:

0.00660303

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000208

AC:

0.000207814

AN:

0.000207814

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000456

AC:

0.000455815

AN:

0.000455815

Gnomad4 OTH

AF:

0.0152

AC:

0.0151515

AN:

0.0151515

Heterozygous variant carriers

196

295

393

491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00466

Hom.:

Bravo

AF:

0.0148

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0383

AC:

148

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.00405

AC:

489

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.13

DEOGEN2

Benign

0.0067

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.45

T;T

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.9

N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

5.5

N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.21

MVP

0.18

MPC

0.11

ClinPred

0.0086

GERP RS

5.0

Varity_R

0.085

gMVP

0.20

Mutation Taster

=100/0

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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