Genetic Variant MEIS1:p.Thr237Met (chr2-66464188-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_002398.3(MEIS1):c.710C>T(p.Thr237Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000243 in 1,603,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

MEIS1
NM_002398.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16

Publications

2 publications found

Variant links:

Genes affected

MEIS1 (HGNC:7000): (Meis homeobox 1) Homeobox genes, of which the most well-characterized category is represented by the HOX genes, play a crucial role in normal development. In addition, several homeoproteins are involved in neoplasia. This gene encodes a homeobox protein belonging to the TALE ('three amino acid loop extension') family of homeodomain-containing proteins. [provided by RefSeq, Jul 2008]

MEIS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.39504066).

BS2

High AC in GnomAdExome4 at 36 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002398.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS1	NM_002398.3	MANE Select	c.710C>T	p.Thr237Met	missense	Exon 7 of 13	NP_002389.1	O00470-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEIS1	ENST00000272369.14	TSL:1 MANE Select	c.710C>T	p.Thr237Met	missense	Exon 7 of 13	ENSP00000272369.8	O00470-1
MEIS1	ENST00000488550.5	TSL:1	c.710C>T	p.Thr237Met	missense	Exon 7 of 11	ENSP00000475161.1	U3KPR8
MEIS1	ENST00000398506.6	TSL:5	c.704C>T	p.Thr235Met	missense	Exon 6 of 11	ENSP00000381518.2	O00470-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000130

AC:

AN:

231156

AF XY:

0.00000803

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000288

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000248

AC:

AN:

1451226

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

720592

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33284

American (AMR)

AF:

0.00

AC:

AN:

43430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25924

East Asian (EAS)

AF:

0.00

AC:

AN:

39248

South Asian (SAS)

AF:

0.00

AC:

AN:

83712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52832

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5532

European-Non Finnish (NFE)

AF:

0.0000307

AC:

AN:

1107212

Other (OTH)

AF:

0.0000167

AC:

AN:

60052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.048

MetaRNN

Benign

0.40

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

1.1

PhyloP100

6.2

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.9

REVEL

Benign

0.28

Sift

Uncertain

0.027

Sift4G

Benign

0.11

Polyphen

0.89

Vest4

0.61

MutPred

0.28

Gain of sheet (P = 0.0166)

MVP

0.66

MPC

1.3

ClinPred

0.62

GERP RS

5.7

Varity_R

0.12

gMVP

0.68

Mutation Taster

=68/32

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over