rs146310692
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBS1BS2_Supporting
The NM_001164507.2(NEB):c.5968G>A(p.Glu1990Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000562 in 1,609,152 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001164507.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.5968G>A | p.Glu1990Lys | missense_variant, splice_region_variant | 46/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.5968G>A | p.Glu1990Lys | missense_variant, splice_region_variant | 46/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.5968G>A | p.Glu1990Lys | missense_variant, splice_region_variant | 46/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.5968G>A | p.Glu1990Lys | missense_variant, splice_region_variant | 46/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.5968G>A | p.Glu1990Lys | missense_variant, splice_region_variant | 46/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00287 AC: 437AN: 152132Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000680 AC: 168AN: 247198Hom.: 1 AF XY: 0.000582 AC XY: 78AN XY: 134114
GnomAD4 exome AF: 0.000321 AC: 468AN: 1456902Hom.: 3 Cov.: 30 AF XY: 0.000270 AC XY: 196AN XY: 724704
GnomAD4 genome ? AF: 0.00287 AC: 437AN: 152250Hom.: 1 Cov.: 32 AF XY: 0.00265 AC XY: 197AN XY: 74438
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 01, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | NEB: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 19, 2021 | - - |
Nemaline myopathy 2 Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 08, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at