11-64804618-T-C

Position:

• chr11-64804618-T-C

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.1549A>G​(p.Lys517Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,002 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MEN1 NM_001370259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38

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 where missense usually causes diseases, MEN1
• BP4: Computational evidence support a benign effect (MetaRNN=0.21357945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEN1	NM_001370259.2	c.1549A>G	p.Lys517Glu	missense_variant	10/10	ENST00000450708.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEN1	ENST00000450708.7	c.1549A>G	p.Lys517Glu	missense_variant	10/10	5	NM_001370259.2	P3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456002 Hom.: 0 Cov.: 43 AF XY: 0.00000276 AC XY: 2 AN XY: 724276

Gnomad4 AFR exome AF: 0.0000299

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	16
DANN	Benign	0.78
DEOGEN2	Benign	0.21	T;.;.;.;.;T;T;T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.81	T;T;.;.;T;.;.;T;.
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.52	D
MutationTaster	Benign	0.81	N;N;N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.070	N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.74	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.97	T;T;T;T;T;T;T;T;T
Polyphen		0.0050, 0.0060	.;B;B;B;B;B;B;B;B
Vest4		0.14
MutPred		0.45		.;.;.;.;.;Loss of methylation at K522 (P = 0.0067);Loss of methylation at K522 (P = 0.0067);Loss of methylation at K522 (P = 0.0067);Loss of methylation at K522 (P = 0.0067);
MVP		0.66
MPC		1.4
ClinPred		0.074	T
GERP RS		2.8
Varity_R		0.15
gMVP		0.55

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: chr11-64572090;