rs200963111
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001164507.2(NEB):c.23141G>A(p.Arg7714Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,599,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.23141G>A | p.Arg7714Gln | missense_variant | 160/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.23141G>A | p.Arg7714Gln | missense_variant | 160/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.23141G>A | p.Arg7714Gln | missense_variant | 160/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.23141G>A | p.Arg7714Gln | missense_variant | 160/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000619 AC: 94AN: 151804Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000142 AC: 32AN: 225430Hom.: 0 AF XY: 0.0000906 AC XY: 11AN XY: 121386
GnomAD4 exome AF: 0.0000801 AC: 116AN: 1447796Hom.: 0 Cov.: 30 AF XY: 0.0000584 AC XY: 42AN XY: 718666
GnomAD4 genome AF: 0.000632 AC: 96AN: 151920Hom.: 0 Cov.: 32 AF XY: 0.000539 AC XY: 40AN XY: 74218
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 27, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | NEB: BP4 - |
Nemaline myopathy 2 Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 17, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 04, 2023 | Variant summary: NEB c.23246G>A (p.Arg7749Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00021 in 256704 control chromosomes, predominantly at a frequency of 0.0021 within the African or African-American subpopulation in the gnomAD database. This frequency is somewhat lower than estimated maximum for a pathogenic variant in NEB causing Nemaline Myopathy 2 (0.0035), allowing no clear conclusions about variant significance. To our knowledge, no occurrence of c.23246G>A in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and the variant as uncertain significance (n = 3) or likely benign (n = 2). Based on the evidence outlined above, the variant was classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2022 | The c.18038G>A (p.R6013Q) alteration is located in exon 133 (coding exon 131) of the NEB gene. This alteration results from a G to A substitution at nucleotide position 18038, causing the arginine (R) at amino acid position 6013 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at