20-36897960-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_015474.4(SAMHD1):c.1609-1G>C variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.00000137 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_015474.4 splice_acceptor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SAMHD1 | NM_015474.4 | c.1609-1G>C | splice_acceptor_variant, intron_variant | Intron 14 of 15 | ENST00000646673.2 | NP_056289.2 | ||
SAMHD1 | NM_001363729.2 | c.1504-1G>C | splice_acceptor_variant, intron_variant | Intron 13 of 14 | NP_001350658.1 | |||
SAMHD1 | NM_001363733.2 | c.1609-1G>C | splice_acceptor_variant, intron_variant | Intron 14 of 15 | NP_001350662.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251328Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135876
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461812Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727206
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Aicardi-Goutieres syndrome 5 Pathogenic:1Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 29, 2020 | This variant has been observed in individual(s) with Aicardi-Goutières syndrome (PMID: 19525956). ClinVar contains an entry for this variant (Variation ID: 126409). Studies have shown that this variant is associated with skipping of exon 15 but is expected to preserve the integrity of the reading-frame (PMID: 19525956). 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 is present in population databases (rs515726143, ExAC 0.006%). This sequence change affects an acceptor splice site in intron 14 of the SAMHD1 gene. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2009 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at