chr18-7012105-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005559.4(LAMA1):c.3397C>T(p.Arg1133Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R1133R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005559.4 stop_gained
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 | UniProt |
---|---|---|---|---|---|---|---|
LAMA1 | NM_005559.4 | c.3397C>T | p.Arg1133Ter | stop_gained | 24/63 | ENST00000389658.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA1 | ENST00000389658.4 | c.3397C>T | p.Arg1133Ter | stop_gained | 24/63 | 1 | NM_005559.4 | P1 | |
LAMA1 | ENST00000579014.5 | n.4412C>T | non_coding_transcript_exon_variant | 23/62 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250388Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135388
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461536Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 727026
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 08, 2022 | The c.3397C>T (p.R1133*) alteration, located in exon 24 (coding exon 24) of the LAMA1 gene, consists of a C to T substitution at nucleotide position 3397. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 1133. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.002% (5/250388) total alleles studied. The highest observed frequency was 0.003% (1/30512) of South Asian alleles. This alteration has been reported compound heterozygous with a missense alteration in LAMA1 in a patient with features consistent with Poretti–Boltshauser syndrome (Powell, 2021). Based on the available evidence, this alteration is classified as pathogenic. - |
Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Sayer Lab, Translational and Clinical Research Institute, Newcastle Unversity | May 21, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at