rs1197561990
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_001164508.2(NEB):c.5344-1G>C variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,168 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 Likely pathogenic (★★).
Frequency
Consequence
NM_001164508.2 splice_acceptor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.5344-1G>C | splice_acceptor_variant | ENST00000427231.7 | NP_001157979.2 | |||
NEB | NM_001164508.2 | c.5344-1G>C | splice_acceptor_variant | ENST00000397345.8 | NP_001157980.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.5344-1G>C | splice_acceptor_variant | 5 | NM_001164508.2 | ENSP00000380505 | P5 | |||
NEB | ENST00000427231.7 | c.5344-1G>C | splice_acceptor_variant | 5 | NM_001164507.2 | ENSP00000416578 | A2 | |||
NEB | ENST00000409198.5 | c.5344-1G>C | splice_acceptor_variant | 5 | ENSP00000386259 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2017 | - - |
Nemaline myopathy 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 22, 2018 | - - |
Arthrogryposis multiplex congenita 6 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 07, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at