rs35654397
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001164507.2(NEB):c.4272G>C(p.Thr1424=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,605,236 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T1424T) has been classified as Likely benign.
Frequency
Consequence
NM_001164507.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.4272G>C | p.Thr1424= | synonymous_variant | 37/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.4272G>C | p.Thr1424= | synonymous_variant | 37/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.4272G>C | p.Thr1424= | synonymous_variant | 37/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.4272G>C | p.Thr1424= | synonymous_variant | 37/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.4272G>C | p.Thr1424= | synonymous_variant | 37/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00254 AC: 386AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00200 AC: 492AN: 246266Hom.: 2 AF XY: 0.00214 AC XY: 286AN XY: 133450
GnomAD4 exome AF: 0.00351 AC: 5096AN: 1452978Hom.: 18 Cov.: 31 AF XY: 0.00346 AC XY: 2492AN XY: 721206
GnomAD4 genome ? AF: 0.00254 AC: 386AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.00263 AC XY: 196AN XY: 74458
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:4
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 09, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 28, 2021 | This variant is associated with the following publications: (PMID: 27535533) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | NEB: BP4, BP7 - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Nemaline myopathy 2 Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 27, 2019 | - - |
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