rs190336010
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6BP7BS1BS2_Supporting
The NM_001164507.2(NEB):āc.19626T>Cā(p.Asp6542=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,607,176 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001164507.2 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.19626T>C | p.Asp6542= | splice_region_variant, synonymous_variant | 126/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.19626T>C | p.Asp6542= | splice_region_variant, synonymous_variant | 126/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.19626T>C | p.Asp6542= | splice_region_variant, synonymous_variant | 126/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.19626T>C | p.Asp6542= | splice_region_variant, synonymous_variant | 126/182 | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00137 AC: 208AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00128 AC: 312AN: 244442Hom.: 1 AF XY: 0.00133 AC XY: 176AN XY: 132448
GnomAD4 exome AF: 0.00162 AC: 2357AN: 1454830Hom.: 5 Cov.: 31 AF XY: 0.00161 AC XY: 1164AN XY: 722834
GnomAD4 genome ? AF: 0.00137 AC: 208AN: 152346Hom.: 0 Cov.: 32 AF XY: 0.00144 AC XY: 107AN XY: 74490
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 10, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 20, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | NEB: BP4, BP7 - |
Nemaline myopathy 2 Uncertain:1Benign:2
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 09, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at