NM_006393.3:c.604G>A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_006393.3(NEBL):c.604G>A(p.Gly202Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,607,228 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006393.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00206 AC: 313AN: 151822Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00208 AC: 521AN: 251076Hom.: 1 AF XY: 0.00187 AC XY: 254AN XY: 135684
GnomAD4 exome AF: 0.00231 AC: 3362AN: 1455290Hom.: 4 Cov.: 30 AF XY: 0.00226 AC XY: 1636AN XY: 724492
GnomAD4 genome AF: 0.00205 AC: 312AN: 151938Hom.: 2 Cov.: 32 AF XY: 0.00183 AC XY: 136AN XY: 74246
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:4
Reported in one individual with adult-onset DCM, one individual with HCM, and one stillbirth case in published literature (Purevjav et al., 2010; Perrot et al., 2016; Sahlin et al., 2019); however, no segregation studies were described; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 45499; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 25987543, 23299917, 25353622, 27186169, 27171814, 27301361, 20951326, 27896284, 21430528, 28654958, 30615648, 23632046) -
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NEBL: BP4, BS1, BS2 -
not specified Uncertain:1Benign:2
The p.Gly202Arg variant in NEBL is classified as benign because it has been identified in 0.3% (24/7206) of Ashkenazi Jewish and in 0.2% (361/128806) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1. -
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NEBL-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Primary dilated cardiomyopathy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at