rs199909967
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_001370259.2(MEN1):c.762G>A(p.Leu254Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,614,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001370259.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MEN1 | NM_001370259.2 | c.762G>A | p.Leu254Leu | synonymous_variant | Exon 4 of 10 | ENST00000450708.7 | NP_001357188.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000211 AC: 53AN: 251278Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135830
GnomAD4 exome AF: 0.000215 AC: 315AN: 1461856Hom.: 0 Cov.: 33 AF XY: 0.000234 AC XY: 170AN XY: 727222
GnomAD4 genome AF: 0.000177 AC: 27AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74496
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Benign:5
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
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not provided Benign:3
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This variant is associated with the following publications: (PMID: 29785153) -
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not specified Benign:2
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Hereditary cancer-predisposing syndrome Benign:2
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This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Hyperparathyroidism Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at