GeneBe

11-64804201-CGGGACCGGGAACCTAGGGTTTGGGTAGAGGTGAGGCCTGTCCCCTTTGGGCTGGGGGCAGAACATGGGCTCAGAGTTGGGGGACTAAGGGCGGAGCCTGGGTCCCCACAAGCGGTCCGAAGTCCCCAGTAGTTCAGAGGCCTTTGCGCTGCCGCTTGAGGAAAGACAGAGTGTAGTCACTAGGGGTGGACACTTTCTGCTTCTTCATCTGCACTTGCGACTGTGCCGTGAGTTGCAGCTTGATGGCGCTCGAGTTGATCTTGGTGGCCACCAGCAGCTCCTTCATGCCCTTCATCTTCTCACTCTGGAAAGTGAGCACTGGACCCTCCGGCGGTGGTGATGCTGTGGGTGCTGGCACCTGAGCCGTGCTGCCACCTTCAGGGCCTCGGGCTGTGCCAGCGACAGTCCCAGGAGGCTTCCGGGGGGGTCCTGACACTGCACCCTGGCCGGTGCCCAGGCCCTTGTCCAGTGCTGGCTTCTTGGGCGGCGGGGGCTCCTCTGGCTTGGACTCCCGCCGTGGGCCCCGCCGCCGGCCTTCCCGGGCTTCCTCGCCCCACGGCTCCTCGGCCTCGGCCGCCTCGGCCTCTCGGCTCACTATGCGCACCTTCTGCCGCACCT-C

Position:

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM4PP5_Moderate

The NM_001370259.2(MEN1):​c.1351-2_*132del variant causes a stop lost, conservative inframe deletion, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MEN1
NM_001370259.2 stop_lost, conservative_inframe_deletion, splice_region

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 0.580
Variant links:
Genes affected
MEN1 (HGNC:7010): (menin 1) This gene encodes menin, a tumor suppressor associated with a syndrome known as multiple endocrine neoplasia type 1. Menin is a scaffold protein that functions in histone modification and epigenetic gene regulation. It is thought to regulate several pathways and processes by altering chromatin structure through the modification of histones. [provided by RefSeq, May 2019]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_001370259.2
PP5
Variant 11-64804201-CGGGACCGGGAACCTAGGGTTTGGGTAGAGGTGAGGCCTGTCCCCTTTGGGCTGGGGGCAGAACATGGGCTCAGAGTTGGGGGACTAAGGGCGGAGCCTGGGTCCCCACAAGCGGTCCGAAGTCCCCAGTAGTTCAGAGGCCTTTGCGCTGCCGCTTGAGGAAAGACAGAGTGTAGTCACTAGGGGTGGACACTTTCTGCTTCTTCATCTGCACTTGCGACTGTGCCGTGAGTTGCAGCTTGATGGCGCTCGAGTTGATCTTGGTGGCCACCAGCAGCTCCTTCATGCCCTTCATCTTCTCACTCTGGAAAGTGAGCACTGGACCCTCCGGCGGTGGTGATGCTGTGGGTGCTGGCACCTGAGCCGTGCTGCCACCTTCAGGGCCTCGGGCTGTGCCAGCGACAGTCCCAGGAGGCTTCCGGGGGGGTCCTGACACTGCACCCTGGCCGGTGCCCAGGCCCTTGTCCAGTGCTGGCTTCTTGGGCGGCGGGGGCTCCTCTGGCTTGGACTCCCGCCGTGGGCCCCGCCGCCGGCCTTCCCGGGCTTCCTCGCCCCACGGCTCCTCGGCCTCGGCCGCCTCGGCCTCTCGGCTCACTATGCGCACCTTCTGCCGCACCT-C is Pathogenic according to our data. Variant chr11-64804201-CGGGACCGGGAACCTAGGGTTTGGGTAGAGGTGAGGCCTGTCCCCTTTGGGCTGGGGGCAGAACATGGGCTCAGAGTTGGGGGACTAAGGGCGGAGCCTGGGTCCCCACAAGCGGTCCGAAGTCCCCAGTAGTTCAGAGGCCTTTGCGCTGCCGCTTGAGGAAAGACAGAGTGTAGTCACTAGGGGTGGACACTTTCTGCTTCTTCATCTGCACTTGCGACTGTGCCGTGAGTTGCAGCTTGATGGCGCTCGAGTTGATCTTGGTGGCCACCAGCAGCTCCTTCATGCCCTTCATCTTCTCACTCTGGAAAGTGAGCACTGGACCCTCCGGCGGTGGTGATGCTGTGGGTGCTGGCACCTGAGCCGTGCTGCCACCTTCAGGGCCTCGGGCTGTGCCAGCGACAGTCCCAGGAGGCTTCCGGGGGGGTCCTGACACTGCACCCTGGCCGGTGCCCAGGCCCTTGTCCAGTGCTGGCTTCTTGGGCGGCGGGGGCTCCTCTGGCTTGGACTCCCGCCGTGGGCCCCGCCGCCGGCCTTCCCGGGCTTCCTCGCCCCACGGCTCCTCGGCCTCGGCCGCCTCGGCCTCTCGGCTCACTATGCGCACCTTCTGCCGCACCT-C is described in ClinVar as [Pathogenic]. Clinvar id is 580649.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MEN1NM_001370259.2 linkuse as main transcriptc.1351-2_*132del stop_lost, conservative_inframe_deletion, splice_region_variant 10/10 ENST00000450708.7 NP_001357188.2
MEN1NM_001370259.2 linkuse as main transcriptc.1355-2_*132del splice_acceptor_variant, 3_prime_UTR_variant, intron_variant 10/10 ENST00000450708.7 NP_001357188.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MEN1ENST00000450708.7 linkuse as main transcriptc.1351-2_*132del stop_lost, conservative_inframe_deletion, splice_region_variant 10/105 NM_001370259.2 ENSP00000394933.3 O00255-2
MEN1ENST00000450708 linkuse as main transcriptc.1355-2_*132del splice_acceptor_variant, 3_prime_UTR_variant, intron_variant 10/105 NM_001370259.2 ENSP00000394933.3 O00255-2

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Multiple endocrine neoplasia, type 1 Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 13, 2018This deletion removes the functionally conserved nuclear localization signal of the MEN1 protein. Experimental studies have shown that disruption of this region abrogates the ability of MEN1 to bind DNA, regulate target gene expression, and inhibit cell proliferation (PMID: 15331604, 16449969). Similar deletions of exon 10 of the MEN1 gene have been reported in an individual affected with multiple endocrine neoplasia type 1 (Invitae) and individuals in the Universal Mutation Database (PMID: 10612827). This variant is a gross deletion of the genomic region encompassing exon 10 of the MEN1 gene. The 5' boundary is located at c.1351-2 and the 3' end of this event is located at c.*132. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product. For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1565634591; hg19: chr11-64571673; API