rs1060499991

Variant names:

• chr11-64804755-C-A
• NM_001370259.2:c.1412G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-64804755-C-A
• chr11-64804755-C-G
• chr11-64804755-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM5 PP2

The NM_001370259.2(MEN1):​c.1412G>T​(p.Trp471Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W471C) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MEN1 NM_001370259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr11-64804754-C-A is described in Lovd as [Pathogenic].
• 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.1412G>T	p.Trp471Leu	missense_variant	Exon 10 of 10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7	c.1412G>T	p.Trp471Leu	missense_variant	Exon 10 of 10	5	NM_001370259.2	ENSP00000394933.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.31	T;.;.;.;.;D;D;D;D
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D;D;.;.;D;.;.;D;.
M_CAP	Pathogenic	0.79	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.66	D
MutationAssessor	Benign	0.69	.;.;.;.;.;N;N;N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.5	N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.54
Sift	Benign	0.42	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.65	T;T;T;T;T;T;T;T;T
Polyphen		0.19, 0.22	.;B;B;B;B;B;B;B;B
Vest4		0.34
MutPred		0.51		.;.;.;.;.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.86
MPC		2.1
ClinPred		0.65	D
GERP RS		4.5
Varity_R		0.20
gMVP		0.74

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: chr11-64572227;