chr3-38045577-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007335.4(DLEC1):ā€‹c.446T>Cā€‹(p.Phe149Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

DLEC1
NM_007335.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.469
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.049874723).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DLEC1NM_007335.4 linkuse as main transcriptc.446T>C p.Phe149Ser missense_variant 2/37 ENST00000308059.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DLEC1ENST00000308059.11 linkuse as main transcriptc.446T>C p.Phe149Ser missense_variant 2/371 NM_007335.4 P2Q9Y238-1
DLEC1ENST00000346219.7 linkuse as main transcriptc.446T>C p.Phe149Ser missense_variant 2/361 A2Q9Y238-3
DLEC1ENST00000440294.6 linkuse as main transcriptn.467T>C non_coding_transcript_exon_variant 2/172

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249134
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135148
show subpopulations
Gnomad AFR exome
AF:
0.000194
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461704
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152126
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.00000828
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 05, 2023The c.446T>C (p.F149S) alteration is located in exon 2 (coding exon 2) of the DLEC1 gene. This alteration results from a T to C substitution at nucleotide position 446, causing the phenylalanine (F) at amino acid position 149 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.0076
.;T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.60
T;T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.050
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.2
L;L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.33
N;N
REVEL
Benign
0.013
Sift
Benign
0.062
T;T
Sift4G
Benign
0.064
T;T
Polyphen
0.33
B;B
Vest4
0.27
MutPred
0.41
Gain of disorder (P = 0.0198);Gain of disorder (P = 0.0198);
MVP
0.35
MPC
0.21
ClinPred
0.042
T
GERP RS
-0.80
Varity_R
0.059
gMVP
0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs766745203; hg19: chr3-38087068; API