11-64809905-G-T

Variant names:

• chr11-64809905-G-T
• NM_001370259.2:c.205C>A

Variant summary

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

The NM_001370259.2(MEN1):​c.205C>A​(p.Pro69Thr) variant causes a missense change. 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEN1 NM_001370259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75

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.205C>A	p.Pro69Thr	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.205C>A	p.Pro69Thr	missense_variant	Exon 2 of 10	5	NM_001370259.2	ENSP00000394933.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1435998 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 712452

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Benign	0.89
DEOGEN2	Uncertain	0.56	D;.;.;.;.;D;D;D;D;D;.;D;.;.
Eigen	Benign	-0.057
Eigen_PC	Benign	0.028
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;T;.;.;T;.;.;T;.;T;T;T;.;T
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Benign	1.2	.;L;L;L;L;L;L;L;L;.;.;.;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.33	N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Pathogenic	0.67
Sift	Benign	0.60	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.70	T;T;T;T;T;T;T;T;T;.;T;T;.;.
Polyphen		0.42, 0.80, 0.47	.;B;P;P;P;P;P;P;P;.;.;.;.;.
Vest4		0.15
MutPred		0.37		Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);Gain of phosphorylation at P69 (P = 0.0349);
MVP		0.80
MPC		1.1
ClinPred		0.49	T
GERP RS		4.0
Varity_R		0.21
gMVP		0.56

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: chr11-64577377;