chr3-38045543-A-T

Position:

• chr3-38045543-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007335.4(DLEC1):​c.412A>T​(p.Ile138Phe) variant causes a missense, splice region 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DLEC1 NM_007335.4 missense, splice_region
• Scores: Splicing: ADA: 0.0003322
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.719

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27978384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLEC1	NM_007335.4	c.412A>T	p.Ile138Phe	missense_variant, splice_region_variant	2/37	ENST00000308059.11	NP_031361.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLEC1	ENST00000308059.11	c.412A>T	p.Ile138Phe	missense_variant, splice_region_variant	2/37	1	NM_007335.4	ENSP00000308597.6
DLEC1	ENST00000346219.7	c.412A>T	p.Ile138Phe	missense_variant, splice_region_variant	2/36	1		ENSP00000315914.5
DLEC1	ENST00000440294.6	n.433A>T		splice_region_variant, non_coding_transcript_exon_variant	2/17	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.412A>T (p.I138F) alteration is located in exon 2 (coding exon 2) of the DLEC1 gene. This alteration results from a A to T substitution at nucleotide position 412, causing the isoleucine (I) at amino acid position 138 to be replaced by a phenylalanine (F). 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	Uncertain	0.34
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.16
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		1.0	D;D
Vest4		0.45
MutPred		0.25		Gain of ubiquitination at K143 (P = 0.086);Gain of ubiquitination at K143 (P = 0.086);
MVP		0.25
MPC		0.53
ClinPred		0.89	D
GERP RS		-2.9
Varity_R		0.12
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00033
dbscSNV1_RF	Benign	0.15
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-38087034;