3-38059754-C-T

Position:

• chr3-38059754-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.013 (38 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (34 hom.)
• Consequence: DLEC1 NM_007335.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.63

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLEC1	NM_007335.4	c.575C>T	p.Ser192Phe	missense_variant	3/37	ENST00000308059.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLEC1	ENST00000308059.11	c.575C>T	p.Ser192Phe	missense_variant	3/37	1	NM_007335.4	P2
DLEC1	ENST00000346219.7	c.575C>T	p.Ser192Phe	missense_variant	3/36	1		A2
DLEC1	ENST00000440294.6	n.596C>T		non_coding_transcript_exon_variant	3/17	2

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1954 AN: 152126 Hom.: 38 Cov.: 32

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

GnomAD3 exomes AF: 0.00320 AC: 798 AN: 249274 Hom.: 16 AF XY: 0.00229 AC XY: 310 AN XY: 135232

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 SAS exome AF: 0.000164

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.: 34 Cov.: 30 AF XY: 0.00136 AC XY: 986 AN XY: 727164

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000262

Gnomad4 OTH exome AF: 0.00402

GnomAD4 genome AF: 0.0129 AC: 1961 AN: 152244 Hom.: 38 Cov.: 32 AF XY: 0.0124 AC XY: 923 AN XY: 74444

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00229 Hom.: 10

Bravo AF: 0.0148

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0383 AC: 148

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.00405 AC: 489

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.13
DEOGEN2	Benign	0.0067	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.45	T;T
MetaRNN	Benign	0.0045	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.9	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.57	T
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	T
GERP RS		5.0
Varity_R		0.085
gMVP		0.20

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

Other links and lift over

dbSNP: rs34012183; hg19: chr3-38101245; COSMIC: COSV57297924; COSMIC: COSV57297924;