NM_007335.4:c.543C>T

Variant names:

• chr3-38045674-C-T
• rs139958483
• NM_007335.4:c.543C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_007335.4(DLEC1):​c.543C>T​(p.Ser181Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,612,726 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (34 hom.)
• Consequence: DLEC1 NM_007335.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.105
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-38045674-C-T is Benign according to our data. Variant chr3-38045674-C-T is described in ClinVar as Benign. ClinVar VariationId is 770885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.105 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 34 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLEC1	NM_007335.4	MANE Select	c.543C>T	p.Ser181Ser	synonymous	Exon 2 of 37	NP_031361.2	Q9Y238-1
	DLEC1	NM_007337.4		c.543C>T	p.Ser181Ser	synonymous	Exon 2 of 36	NP_031363.2	Q9Y238-3
	DLEC1	NM_001321153.2		c.543C>T	p.Ser181Ser	synonymous	Exon 2 of 37	NP_001308082.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLEC1	ENST00000308059.11	TSL:1 MANE Select	c.543C>T	p.Ser181Ser	synonymous	Exon 2 of 37	ENSP00000308597.6	Q9Y238-1
	DLEC1	ENST00000346219.7	TSL:1	c.543C>T	p.Ser181Ser	synonymous	Exon 2 of 36	ENSP00000315914.5	Q9Y238-3
	DLEC1	ENST00000896006.1		c.543C>T	p.Ser181Ser	synonymous	Exon 2 of 37	ENSP00000566065.1

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 469 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00556

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00297 AC: 733 AN: 247180 AF XY: 0.00291

Gnomad AFR exome AF: 0.000780

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00112

Gnomad NFE exome AF: 0.00552

Gnomad OTH exome AF: 0.00267

GnomAD4 exome AF: 0.00547 AC: 7989 AN: 1460500 Hom.: 34 Cov.: 31 AF XY: 0.00531 AC XY: 3860 AN XY: 726552

African (AFR) AF: 0.000569 AC: 19 AN: 33372

American (AMR) AF: 0.00157 AC: 70 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.0000768 AC: 2 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.000279 AC: 24 AN: 86106

European-Finnish (FIN) AF: 0.000880 AC: 47 AN: 53396

Middle Eastern (MID) AF: 0.000699 AC: 4 AN: 5724

European-Non Finnish (NFE) AF: 0.00681 AC: 7565 AN: 1111448

Other (OTH) AF: 0.00428 AC: 258 AN: 60328

GnomAD4 genome AF: 0.00308 AC: 469 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.00259 AC XY: 193 AN XY: 74426

African (AFR) AF: 0.00118 AC: 49 AN: 41546

American (AMR) AF: 0.00157 AC: 24 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00556 AC: 378 AN: 68002

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00411 Hom.: 0

Bravo AF: 0.00317

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00496

EpiControl AF: 0.00576

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs139958483; hg19: chr3-38087165;