rs372104796

Variant names:

• chr3-38108411-G-A
• rs372104796
• NM_007335.4:c.3025G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-38108411-G-A
• chr3-38108411-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_007335.4(DLEC1):​c.3025G>A​(p.Gly1009Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,613,704 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: DLEC1 NM_007335.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68
• Publications: 1 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]

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

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.3025G>A	p.Gly1009Arg	missense	Exon 21 of 37	NP_031361.2	Q9Y238-1
	DLEC1	NM_007337.4		c.3025G>A	p.Gly1009Arg	missense	Exon 21 of 36	NP_031363.2	Q9Y238-3
	DLEC1	NM_001321153.2		c.3025G>A	p.Gly1009Arg	missense	Exon 21 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.3025G>A	p.Gly1009Arg	missense	Exon 21 of 37	ENSP00000308597.6	Q9Y238-1
	DLEC1	ENST00000346219.7	TSL:1	c.3025G>A	p.Gly1009Arg	missense	Exon 21 of 36	ENSP00000315914.5	Q9Y238-3
	DLEC1	ENST00000896006.1		c.3025G>A	p.Gly1009Arg	missense	Exon 21 of 37	ENSP00000566065.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152186 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000724 AC: 18 AN: 248692 AF XY: 0.0000815

Gnomad AFR exome AF: 0.0000650

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000975

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000114 AC: 166 AN: 1461518 Hom.: 0 Cov.: 31 AF XY: 0.000120 AC XY: 87 AN XY: 727028

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.000112 AC: 5 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000135 AC: 150 AN: 1111868

Other (OTH) AF: 0.0000994 AC: 6 AN: 60384

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152186 Hom.: 1 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74340

African (AFR) AF: 0.000121 AC: 5 AN: 41438

American (AMR) AF: 0.000262 AC: 4 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.000102

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.0000579 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.53		Gain of solvent accessibility (P = 0.019)
MVP		0.86
MPC		0.57
ClinPred		0.92	D
GERP RS		4.9
Varity_R		0.82
gMVP		0.65
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: 2

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

Other links and lift over

dbSNP: rs372104796; hg19: chr3-38149902; COSMIC: COSV100342015; COSMIC: COSV100342015;