rs1555166619

Positions:

• chr11-64809926-T-A
• chr11-64809926-T-C
• chr11-64809926-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001370259.2(MEN1):​c.184A>T​(p.Thr62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T62P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MEN1 NM_001370259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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 1 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=0.19251397).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEN1	NM_001370259.2	c.184A>T	p.Thr62Ser	missense_variant	2/10	ENST00000450708.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEN1	ENST00000450708.7	c.184A>T	p.Thr62Ser	missense_variant	2/10	5	NM_001370259.2	P3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Uncertain	0.49	T;.;.;.;.;D;D;D;D;D;.;D;.;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.63	T;T;.;.;T;.;.;T;.;T;T;T;.;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	0.34	.;N;N;N;N;N;N;N;N;.;.;.;.;.
MutationTaster	Benign	0.99	N;N;N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.49	N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.39
Sift	Benign	0.65	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.89	T;T;T;T;T;T;T;T;T;.;T;T;.;.
Polyphen		0.0030, 0.090	.;B;B;B;B;B;B;B;B;.;.;.;.;.
Vest4		0.081
MutPred		0.32		Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);
MVP		0.80
MPC		0.93
ClinPred		0.24	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr11-64577398;