chr3-38039272-C-T

Variant names:

• chr3-38039272-C-T
• rs186486591
• NM_007335.4:c.47C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_007335.4(DLEC1):​c.47C>T​(p.Thr16Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,613,788 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00056 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: DLEC1 NM_007335.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0650
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037665367).
• BP6: Variant 3-38039272-C-T is Benign according to our data. Variant chr3-38039272-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 710796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.47C>T	p.Thr16Ile	missense	Exon 1 of 37	NP_031361.2	Q9Y238-1
	DLEC1	NM_007337.4		c.47C>T	p.Thr16Ile	missense	Exon 1 of 36	NP_031363.2	Q9Y238-3
	DLEC1	NM_001321153.2		c.47C>T	p.Thr16Ile	missense	Exon 1 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.47C>T	p.Thr16Ile	missense	Exon 1 of 37	ENSP00000308597.6	Q9Y238-1
	DLEC1	ENST00000346219.7	TSL:1	c.47C>T	p.Thr16Ile	missense	Exon 1 of 36	ENSP00000315914.5	Q9Y238-3
	DLEC1	ENST00000896006.1		c.47C>T	p.Thr16Ile	missense	Exon 1 of 37	ENSP00000566065.1

Frequencies

GnomAD3 genomes AF: 0.000571 AC: 87 AN: 152236 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000897 AC: 223 AN: 248498 AF XY: 0.000779

Gnomad AFR exome AF: 0.000711

Gnomad AMR exome AF: 0.00542

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.000289 AC: 422 AN: 1461434 Hom.: 0 Cov.: 30 AF XY: 0.000286 AC XY: 208 AN XY: 727028

African (AFR) AF: 0.000209 AC: 7 AN: 33476

American (AMR) AF: 0.00589 AC: 263 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000105 AC: 117 AN: 1111762

Other (OTH) AF: 0.000265 AC: 16 AN: 60380

GnomAD4 genome AF: 0.000564 AC: 86 AN: 152354 Hom.: 1 Cov.: 33 AF XY: 0.000456 AC XY: 34 AN XY: 74500

African (AFR) AF: 0.000289 AC: 12 AN: 41586

American (AMR) AF: 0.00346 AC: 53 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000324 Hom.: 1

Bravo AF: 0.000782

ESP6500AA AF: 0.000954 AC: 4

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.000826 AC: 100

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely 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
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.5
DANN	Benign	0.97
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.065
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.029
Sift	Benign	0.072	T
Sift4G	Benign	0.088	T
Polyphen		0.10	B
Vest4		0.086
MVP		0.14
MPC		0.14
ClinPred		0.00085	T
GERP RS		0.72
PromoterAI		0.091	Neutral
Varity_R		0.045
gMVP		0.16
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: rs186486591; hg19: chr3-38080763;