22-20982361-G-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_006767.4(LZTR1):c.-11G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,546,152 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_006767.4 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LZTR1 | NM_006767.4 | c.-11G>A | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 21 | ENST00000646124.2 | NP_006758.2 | ||
LZTR1 | NM_006767.4 | c.-11G>A | 5_prime_UTR_variant | Exon 1 of 21 | ENST00000646124.2 | NP_006758.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LZTR1 | ENST00000646124 | c.-11G>A | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 21 | NM_006767.4 | ENSP00000496779.1 | ||||
LZTR1 | ENST00000646124 | c.-11G>A | 5_prime_UTR_variant | Exon 1 of 21 | NM_006767.4 | ENSP00000496779.1 |
Frequencies
GnomAD3 genomes AF: 0.000965 AC: 147AN: 152262Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000913 AC: 134AN: 146760Hom.: 0 AF XY: 0.000911 AC XY: 72AN XY: 79076
GnomAD4 exome AF: 0.00138 AC: 1925AN: 1393772Hom.: 2 Cov.: 32 AF XY: 0.00133 AC XY: 911AN XY: 687012
GnomAD4 genome AF: 0.000965 AC: 147AN: 152380Hom.: 0 Cov.: 33 AF XY: 0.000993 AC XY: 74AN XY: 74516
ClinVar
Submissions by phenotype
not provided Benign:2Other:1
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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. -
not specified Benign:1
Variant summary: LZTR1 c.-11G>A alters a non-conserved nucleotide located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.00091 in 146760 control chromosomes. The observed variant frequency is approximately 183 fold of the estimated maximal expected allele frequency for a pathogenic variant in LZTR1 causing Noonan Syndrome and Related Conditions phenotype (5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.-11G>A in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at