rs141031435
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001351169.2(NT5C2):c.1665G>T(p.Glu555Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,607,780 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001351169.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NT5C2 | NM_001351169.2 | c.1665G>T | p.Glu555Asp | missense_variant | 19/19 | ENST00000404739.8 | |
CNNM2 | NM_017649.5 | c.*12513C>A | 3_prime_UTR_variant | 8/8 | ENST00000369878.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NT5C2 | ENST00000404739.8 | c.1665G>T | p.Glu555Asp | missense_variant | 19/19 | 1 | NM_001351169.2 | P1 | |
CNNM2 | ENST00000369878.9 | c.*12513C>A | 3_prime_UTR_variant | 8/8 | 1 | NM_017649.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152018Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000184 AC: 45AN: 245124Hom.: 0 AF XY: 0.000197 AC XY: 26AN XY: 132308
GnomAD4 exome AF: 0.000377 AC: 549AN: 1455762Hom.: 1 Cov.: 30 AF XY: 0.000366 AC XY: 265AN XY: 723888
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152018Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74238
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 45 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 555 of the NT5C2 protein (p.Glu555Asp). This variant is present in population databases (rs141031435, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with NT5C2-related conditions. ClinVar contains an entry for this variant (Variation ID: 541766). 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"). 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