chr15-22812248-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_144599.5(NIPA1):c.312G>A(p.Pro104Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,607,748 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_144599.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000585 AC: 89AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000633 AC: 159AN: 251228Hom.: 0 AF XY: 0.000582 AC XY: 79AN XY: 135824
GnomAD4 exome AF: 0.00121 AC: 1767AN: 1455426Hom.: 5 Cov.: 29 AF XY: 0.00119 AC XY: 864AN XY: 724462
GnomAD4 genome AF: 0.000584 AC: 89AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.000537 AC XY: 40AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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Hereditary spastic paraplegia 6 Benign:2
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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
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not specified Benign:1
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
NIPA1-related disorder Benign:1
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). -
Hereditary spastic paraplegia Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at