rs763800487

Variant names:

• chr3-38039238-A-C
• rs763800487
• NM_007335.4:c.13A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-38039238-A-C
• chr3-38039238-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007335.4(DLEC1):​c.13A>C​(p.Ser5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S5G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLEC1 NM_007335.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603

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 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=0.03999111).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLEC1	NM_007335.4	c.13A>C	p.Ser5Arg	missense_variant	Exon 1 of 37	ENST00000308059.11	NP_031361.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLEC1	ENST00000308059.11	c.13A>C	p.Ser5Arg	missense_variant	Exon 1 of 37	1	NM_007335.4	ENSP00000308597.6
DLEC1	ENST00000346219.7	c.13A>C	p.Ser5Arg	missense_variant	Exon 1 of 36	1		ENSP00000315914.5
DLEC1	ENST00000440294.6	n.34A>C		non_coding_transcript_exon_variant	Exon 1 of 17	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.40
DANN	Benign	0.57
DEOGEN2	Benign	0.0030	.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.32	T;T
M_CAP	Benign	0.00083	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.76	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.57	N;N
REVEL	Benign	0.025
Sift	Benign	0.45	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;B
Vest4		0.11
MutPred		0.17		Gain of glycosylation at S5 (P = 0.002);Gain of glycosylation at S5 (P = 0.002);
MVP		0.055
MPC		0.12
ClinPred		0.037	T
GERP RS		-10
Varity_R		0.040
gMVP		0.19

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

Other links and lift over

dbSNP: rs763800487; hg19: chr3-38080729;