rs72846108
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_001351169.2(NT5C2):āc.141G>Cā(p.Lys47Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,583,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K47E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001351169.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NT5C2 | NM_001351169.2 | c.141G>C | p.Lys47Asn | missense_variant | 4/19 | ENST00000404739.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NT5C2 | ENST00000404739.8 | c.141G>C | p.Lys47Asn | missense_variant | 4/19 | 1 | NM_001351169.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000129 AC: 27AN: 208902Hom.: 0 AF XY: 0.000160 AC XY: 18AN XY: 112244
GnomAD4 exome AF: 0.000171 AC: 245AN: 1430748Hom.: 0 Cov.: 29 AF XY: 0.000173 AC XY: 123AN XY: 709292
GnomAD4 genome AF: 0.0000919 AC: 14AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74474
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2021 | The c.141G>C (p.K47N) alteration is located in exon 1 (coding exon 1) of the NT5C2 gene. This alteration results from a G to C substitution at nucleotide position 141, causing the lysine (K) at amino acid position 47 to be replaced by an asparagine (N). The p.K47N alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary spastic paraplegia 45 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 943906). This variant has not been reported in the literature in individuals affected with NT5C2-related conditions. This variant is present in population databases (rs72846108, gnomAD 0.03%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 47 of the NT5C2 protein (p.Lys47Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at