11-64809895-G-C

Variant names:

• chr11-64809895-G-C
• NM_001370259.2:c.215C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001370259.2(MEN1):​c.215C>G​(p.Pro72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MEN1 NM_001370259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the MEN1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 113 curated pathogenic missense variants (we use a threshold of 10). The gene has 20 curated benign missense variants. Trascript score misZ: 4.1921 (above the threshold of 3.09). GenCC associations: The gene is linked to multiple endocrine neoplasia type 1, pituitary gigantism, familial isolated hyperparathyroidism.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEN1	NM_001370259.2	c.215C>G	p.Pro72Arg	missense_variant	Exon 2 of 10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7	c.215C>G	p.Pro72Arg	missense_variant	Exon 2 of 10	5	NM_001370259.2	ENSP00000394933.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.57	D;.;.;.;.;D;D;D;D;D;.;D;.;.
Eigen	Benign	-0.036
Eigen_PC	Benign	0.072
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D;D;.;.;D;.;.;D;.;D;D;D;.;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.50	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Benign	2.0	.;M;M;M;M;M;M;M;M;.;.;.;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Pathogenic	0.66
Sift	Benign	0.29	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.49	T;T;T;T;T;T;T;T;T;.;T;T;.;.
Polyphen		1.0, 0.027	.;D;B;B;B;D;D;D;D;.;.;.;.;.
Vest4		0.36
MutPred		0.47		Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);Loss of catalytic residue at P71 (P = 0.0165);
MVP		0.89
MPC		1.2
ClinPred		0.66	D
GERP RS		4.9
Varity_R		0.46
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-64577367;