11-64804661-C-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_001370259.2(MEN1):āc.1506G>Cā(p.Lys502Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,599,226 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 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.1506G>C | p.Lys502Asn | missense_variant | Exon 10 of 10 | ENST00000450708.7 | NP_001357188.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000136 AC: 3AN: 221350Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 122352
GnomAD4 exome AF: 0.00000415 AC: 6AN: 1447024Hom.: 0 Cov.: 42 AF XY: 0.00000278 AC XY: 2AN XY: 719648
GnomAD4 genome AF: 0.000112 AC: 17AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74356
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
This alteration is classified as 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. -
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Multiple endocrine neoplasia, type 1 Benign:2
This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -
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not provided Uncertain:1
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MEN1-related disorder Uncertain:1
The MEN1 c.1521G>C variant is predicted to result in the amino acid substitution p.Lys507Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.032% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-64572133-C-G) and is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/403821/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at