rs143537405
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PM1PM2BP4_StrongBP6BS1
The NM_198586.3(NHLRC1):c.422T>C(p.Val141Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000228 in 1,613,006 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V141V) has been classified as Likely benign.
Frequency
Consequence
NM_198586.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHLRC1 | NM_198586.3 | c.422T>C | p.Val141Ala | missense_variant | 1/1 | ENST00000340650.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHLRC1 | ENST00000340650.6 | c.422T>C | p.Val141Ala | missense_variant | 1/1 | NM_198586.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00123 AC: 187AN: 152072Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000317 AC: 78AN: 246324Hom.: 0 AF XY: 0.000239 AC XY: 32AN XY: 134096
GnomAD4 exome AF: 0.000124 AC: 181AN: 1460816Hom.: 0 Cov.: 31 AF XY: 0.0000991 AC XY: 72AN XY: 726760
GnomAD4 genome ? AF: 0.00123 AC: 187AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93AN XY: 74396
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 05, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 25, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 18, 2018 | The p.V141A variant (also known as c.422T>C), located in coding exon 1 of the NHLRC1 gene, results from a T to C substitution at nucleotide position 422. The valine at codon 141 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Lafora disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
NHLRC1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 09, 2022 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at