rs267607547
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP2PP5_Moderate
The NM_170707.4(LMNA):āc.1619T>Cā(p.Met540Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,401,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M540I) has been classified as Pathogenic.
Frequency
Consequence
NM_170707.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMNA | NM_170707.4 | c.1619T>C | p.Met540Thr | missense_variant | 10/12 | ENST00000368300.9 | |
LMNA | NM_005572.4 | c.1619T>C | p.Met540Thr | missense_variant | 10/10 | ENST00000677389.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMNA | ENST00000368300.9 | c.1619T>C | p.Met540Thr | missense_variant | 10/12 | 1 | NM_170707.4 | P1 | |
LMNA | ENST00000677389.1 | c.1619T>C | p.Met540Thr | missense_variant | 10/10 | NM_005572.4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 7.13e-7 AC: 1AN: 1401634Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 691454
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hutchinson-Gilford syndrome Pathogenic:1Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
not provided Other:1
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at