6-42960777-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_018960.6(GNMT):c.10A>G(p.Ser4Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000195 in 1,538,150 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 (★). Synonymous variant affecting the same amino acid position (i.e. S4S) has been classified as Likely benign.
Frequency
Consequence
NM_018960.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNMT | NM_018960.6 | c.10A>G | p.Ser4Gly | missense_variant | 1/6 | ENST00000372808.4 | |
CNPY3-GNMT | NR_134890.2 | n.340-1985A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNMT | ENST00000372808.4 | c.10A>G | p.Ser4Gly | missense_variant | 1/6 | 1 | NM_018960.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000135 AC: 2AN: 148376Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 79968
GnomAD4 exome AF: 0.00000144 AC: 2AN: 1385906Hom.: 0 Cov.: 33 AF XY: 0.00000147 AC XY: 1AN XY: 681952
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74384
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 15, 2019 | 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. This variant has not been reported in the literature in individuals with GNMT-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces serine with glycine at codon 4 of the GNMT protein (p.Ser4Gly). The serine residue is highly conserved and there is a small physicochemical difference between serine and glycine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at