11-64805085-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001370259.2(MEN1):c.1299T>C(p.His433His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,614,144 control chromosomes in the GnomAD database, including 800,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 72937 hom., cov: 36)

Exomes 𝑓: 1.0 ( 727809 hom. )

Consequence

MEN1
NM_001370259.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.301

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 11-64805085-A-G is Benign according to our data. Variant chr11-64805085-A-G is described in ClinVar as [Benign]. Clinvar id is 167288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805085-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.301 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEN1	NM_001370259.2 link	c.1299T>C	p.His433His	synonymous_variant	Exon 9 of 10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7 link	c.1299T>C	p.His433His	synonymous_variant	Exon 9 of 10	5	NM_001370259.2	ENSP00000394933.3		O00255-2

Frequencies

GnomAD3 genomes

AF:

0.978

AC:

148864

AN:

152214

Hom.:

72884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.923

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.993

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.984

GnomAD2 exomes

AF:

0.994

AC:

249724

AN:

251190

AF XY:

0.996

show subpopulations

Gnomad AFR exome

AF:

0.919

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.996

GnomAD4 exome

AF:

0.998

AC:

1458581

AN:

1461812

Hom.:

727809

Cov.:

AF XY:

0.998

AC XY:

725854

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.919

AC:

30772

AN:

33480

Gnomad4 AMR exome

AF:

0.997

AC:

44569

AN:

44714

Gnomad4 ASJ exome

AF:

1.00

AC:

26134

AN:

26134

Gnomad4 EAS exome

AF:

1.00

AC:

39698

AN:

39700

Gnomad4 SAS exome

AF:

1.00

AC:

86244

AN:

86258

Gnomad4 FIN exome

AF:

1.00

AC:

53364

AN:

53366

Gnomad4 NFE exome

AF:

1.00

AC:

1111954

AN:

1112004

Gnomad4 Remaining exome

AF:

0.995

AC:

60103

AN:

60396

Heterozygous variant carriers

189

379

568

758

947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

21668

43336

65004

86672

108340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.978

AC:

148976

AN:

152332

Hom.:

72937

Cov.:

AF XY:

0.978

AC XY:

72873

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.923

AC:

0.923044

AN:

0.923044

Gnomad4 AMR

AF:

0.993

AC:

0.992685

AN:

0.992685

Gnomad4 ASJ

AF:

1.00

AC:

AN:

Gnomad4 EAS

AF:

1.00

AC:

AN:

Gnomad4 SAS

AF:

1.00

AC:

AN:

Gnomad4 FIN

AF:

1.00

AC:

AN:

Gnomad4 NFE

AF:

1.00

AC:

0.999824

AN:

0.999824

Gnomad4 OTH

AF:

0.984

AC:

0.983917

AN:

0.983917

Heterozygous variant carriers

166

333

499

666

832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.991

Hom.:

34255

Bravo

AF:

0.975

Asia WGS

AF:

0.995

AC:

3461

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Multiple endocrine neoplasia, type 1

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 29, 2019

Color Diagnostics, LLC DBA Color Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 05, 2024

Myriad Genetics, Inc.

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

not specified

Benign:2

Jun 22, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 23, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.1314T>C in exon 10 of MEN1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 99.99% (66603/66608) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs540012). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.0

DANN

Benign

0.54

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over