rs199980022
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001330078.2(NRXN1):c.3032C>T(p.Thr1011Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,610,564 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T1011T) has been classified as Likely benign.
Frequency
Consequence
NM_001330078.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRXN1 | NM_001330078.2 | c.3032C>T | p.Thr1011Met | missense_variant | 15/23 | ENST00000401669.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRXN1 | ENST00000401669.7 | c.3032C>T | p.Thr1011Met | missense_variant | 15/23 | 5 | NM_001330078.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246114Hom.: 0 AF XY: 0.0000225 AC XY: 3AN XY: 133530
GnomAD4 exome AF: 0.0000206 AC: 30AN: 1458396Hom.: 0 Cov.: 31 AF XY: 0.0000207 AC XY: 15AN XY: 725188
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 28, 2012 | p.Thr1051Met (ACG>ATG): c.3152 C>T in exon 16 of the NRXN1 gene (NM_001135659.1) The Thr1051Met missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Thr1051Met in approximately 6,300 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a polar Threonine residue is replaced by a non-polar Methionine residue. It alters a highly conserved position in the fifth laminin G-like domain. However, missense mutations have not been previously reported in this region of the protein, and multiple in silico algorithms predict Thr1051Met is likely benign. Therefore, based on the currently available information, it is unclear whether Thr1051Met is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). - |
Pitt-Hopkins-like syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 06, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1051 of the NRXN1 protein (p.Thr1051Met). This variant is present in population databases (rs199980022, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 206255). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at