rs75959644
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006767.4(LZTR1):c.1353+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,610,426 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_006767.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LZTR1 | NM_006767.4 | c.1353+8C>G | splice_region_variant, intron_variant | ENST00000646124.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LZTR1 | ENST00000646124.2 | c.1353+8C>G | splice_region_variant, intron_variant | NM_006767.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000926 AC: 141AN: 152214Hom.: 2 Cov.: 34
GnomAD3 exomes AF: 0.00190 AC: 467AN: 245996Hom.: 10 AF XY: 0.00173 AC XY: 231AN XY: 133696
GnomAD4 exome AF: 0.000587 AC: 856AN: 1458094Hom.: 13 Cov.: 31 AF XY: 0.000565 AC XY: 410AN XY: 725210
GnomAD4 genome ? AF: 0.000919 AC: 140AN: 152332Hom.: 2 Cov.: 34 AF XY: 0.00109 AC XY: 81AN XY: 74478
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 30, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 11, 2017 | Variant summary: The LZTR1 c.1353+8C>G variant involves the alteration of a non-conserved intronic nucleotide and 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 203/112292 control chromosomes (3 homozygotes), predominantly in the East Asian cohort at a frequency of 0.024024 (197/8200). This frequency is about 4805 times the estimated maximal expected allele frequency of a pathogenic LZTR1 variant (0.000005), suggesting this is likely a benign polymorphism found primarily in population(s) of East Asian origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 14, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Noonan syndrome and Noonan-related syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jun 17, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at