11-64809784-T-G

Position:

• chr11-64809784-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001370259.2(MEN1):​c.326A>C​(p.Glu109Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MEN1 NM_001370259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06

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]

MEN1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MEN1. . Trascript score misZ 4.1921 (greater than threshold 3.09). GenCC has associacion of gene with multiple endocrine neoplasia type 1, pituitary gigantism, familial isolated hyperparathyroidism.
• BP4: Computational evidence support a benign effect (MetaRNN=0.2728942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEN1	NM_001370259.2	c.326A>C	p.Glu109Ala	missense_variant	2/10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7	c.326A>C	p.Glu109Ala	missense_variant	2/10	5	NM_001370259.2	ENSP00000394933.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.60	D;.;.;.;.;D;D;D;D;D;.;D;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.028
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.90	D;D;.;.;D;.;.;D;.;D;D;D;.;D
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Pathogenic	0.91	D
MutationAssessor	Benign	1.2	.;L;L;L;L;L;L;L;L;.;.;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.49
Sift	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.66	T;T;T;T;T;T;T;T;T;.;T;T;.;.
Polyphen		0.013, 0.092, 0.11	.;B;B;B;B;B;B;B;B;.;.;.;.;.
Vest4		0.14
MutPred		0.51		Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);
MVP		0.70
MPC		1.1
ClinPred		0.65	D
GERP RS		5.0
Varity_R		0.45
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: chr11-64577256;