chr19-45488913-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_005619.5(RTN2):c.1315G>A(p.Val439Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,609,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005619.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTN2 | NM_005619.5 | c.1315G>A | p.Val439Met | missense_variant | 7/11 | ENST00000245923.9 | |
RTN2 | NM_206900.3 | c.1096G>A | p.Val366Met | missense_variant | 6/10 | ||
RTN2 | NM_206901.3 | c.295G>A | p.Val99Met | missense_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTN2 | ENST00000245923.9 | c.1315G>A | p.Val439Met | missense_variant | 7/11 | 1 | NM_005619.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000167 AC: 4AN: 240216Hom.: 0 AF XY: 0.00000770 AC XY: 1AN XY: 129870
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1457404Hom.: 0 Cov.: 33 AF XY: 0.0000262 AC XY: 19AN XY: 724506
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74488
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 13, 2024 | Variant summary: SLC12A3 c.1315G>A (p.Gly439Ser) results in a non-conservative amino acid change located in the Amino acid permease/ SLC12A domain (IPR004841) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 250818 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SLC12A3 causing Familial Hypokalemia-Hypomagnesemia (0.00016 vs ND), allowing no conclusion about variant significance. c.1315G>A has been reported in the literature in multiple individuals affected with Familial Hypokalemia-Hypomagnesemia. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 586601). Based on the evidence outlined above, the variant was classified as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at