rs387907365
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PS1_ModeratePP3
The NM_001105206.3(LAMA4):c.2849C>T(p.Pro950Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,552 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 Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Synonymous variant affecting the same amino acid position (i.e. P950P) has been classified as Likely benign.
Frequency
Consequence
NM_001105206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.2849C>T | p.Pro950Leu | missense_variant | 22/39 | ENST00000230538.12 | |
LOC107986633 | XR_001744299.2 | n.440-14433G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.2849C>T | p.Pro950Leu | missense_variant | 22/39 | 1 | NM_001105206.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152004Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251150Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135716
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461548Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727102
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74240
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1JJ Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 2023 | 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. Experimental studies have shown that this missense change affects LAMA4 function (PMID: 17646580). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 50370). This variant is also known as c.2849C>T (p.Pro950Leu). This missense change has been observed in individual(s) with clinical features of LAMA4-related conditions (PMID: 17646580, 31514951). This variant is present in population databases (rs387907365, gnomAD 0.004%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 943 of the LAMA4 protein (p.Pro943Leu). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 31, 2007 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at