3-38107708-C-T

Variant names:

• chr3-38107708-C-T
• NM_007335.4:c.2989C>T

Variant summary

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

The NM_007335.4(DLEC1):​c.2989C>T​(p.Leu997Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLEC1 NM_007335.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67

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]

ACAA1 (HGNC:82): (acetyl-CoA acyltransferase 1) This gene encodes an enzyme operative in the beta-oxidation system of the peroxisomes. Deficiency of this enzyme leads to pseudo-Zellweger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

LOC105377033 (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=0.39972383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLEC1	NM_007335.4	c.2989C>T	p.Leu997Phe	missense_variant	Exon 20 of 37	ENST00000308059.11	NP_031361.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLEC1	ENST00000308059.11	c.2989C>T	p.Leu997Phe	missense_variant	Exon 20 of 37	1	NM_007335.4	ENSP00000308597.6
DLEC1	ENST00000346219.7	c.2989C>T	p.Leu997Phe	missense_variant	Exon 20 of 36	1		ENSP00000315914.5
ACAA1	ENST00000451419.1	n.300-3915G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2989C>T (p.L997F) alteration is located in exon 20 (coding exon 20) of the DLEC1 gene. This alteration results from a C to T substitution at nucleotide position 2989, causing the leucine (L) at amino acid position 997 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	Benign	0.18
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.074	T;T
Polyphen		1.0	D;D
Vest4		0.33
MutPred		0.46		Loss of catalytic residue at L997 (P = 0.1399);Loss of catalytic residue at L997 (P = 0.1399);
MVP		0.66
MPC		0.37
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.16
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-38149199;