rs1131690797

Variant names:

• chr18-58341753-C-G
• NM_001144967.3:c.1333C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-58341753-C-G
• chr18-58341753-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144967.3(NEDD4L):​c.1333C>G​(p.Arg445Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEDD4L NM_001144967.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.66

Genes affected

NEDD4L (HGNC:7728): (NEDD4 like E3 ubiquitin protein ligase) This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD4L	NM_001144967.3	c.1333C>G	p.Arg445Gly	missense_variant	Exon 15 of 31	ENST00000400345.8	NP_001138439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD4L	ENST00000400345.8	c.1333C>G	p.Arg445Gly	missense_variant	Exon 15 of 31	1	NM_001144967.3	ENSP00000383199.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	.;T;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;.;D;D;D;.;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.47	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	.;L;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.1	N;N;N;N;N;N;.;N;N;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0030	D;T;D;T;D;T;.;D;T;.
Sift4G	Benign	0.38	T;T;T;T;T;T;T;T;T;.
Polyphen		0.99	D;B;P;.;.;P;B;.;.;.
Vest4		0.79
MutPred		0.29		.;Gain of glycosylation at S446 (P = 0.0552);.;.;.;.;.;.;.;.;
MVP		0.83
MPC		1.8
ClinPred		0.82	D
GERP RS		5.8
Varity_R		0.17
gMVP		0.57

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: chr18-56008985;