rs200945025
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP6BS1BS2
The NM_001164507.2(NEB):c.21838G>A(p.Asp7280Asn) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,610,212 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D7280D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001164507.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.21838G>A | p.Asp7280Asn | missense_variant, splice_region_variant | 147/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.21838G>A | p.Asp7280Asn | missense_variant, splice_region_variant | 147/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.21838G>A | p.Asp7280Asn | missense_variant, splice_region_variant | 147/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.21838G>A | p.Asp7280Asn | missense_variant, splice_region_variant | 147/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152182Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000940 AC: 231AN: 245686Hom.: 1 AF XY: 0.000616 AC XY: 82AN XY: 133176
GnomAD4 exome AF: 0.000180 AC: 263AN: 1457912Hom.: 0 Cov.: 30 AF XY: 0.000138 AC XY: 100AN XY: 725158
GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152300Hom.: 2 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74474
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 05, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 25, 2020 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 05, 2022 | The c.16735G>A (p.D5579N) alteration is located in exon 120 (coding exon 118) of the NEB gene. This alteration results from a G to A substitution at nucleotide position 16735, causing the aspartic acid (D) at amino acid position 5579 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
NEB-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 13, 2020 | 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). - |
Nemaline myopathy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at