dbSNP rs372906440: MECOM:p.Val1239Leu (chr3-169084914-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004991.4(MECOM):c.3715G>T(p.Val1239Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. V1239I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MECOM
NM_004991.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.41

Publications

0 publications found

Variant links:

Genes affected

MECOM (HGNC:3498): (MDS1 and EVI1 complex locus) The protein encoded by this gene is a transcriptional regulator and oncoprotein that may be involved in hematopoiesis, apoptosis, development, and cell differentiation and proliferation. The encoded protein can interact with CTBP1, SMAD3, CREBBP, KAT2B, MAPK8, and MAPK9. This gene can undergo translocation with the AML1 gene, resulting in overexpression of this gene and the onset of leukemia. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

MECOM Gene-Disease associations (from GenCC):

MECOM-associated syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
radioulnar synostosis with amegakaryocytic thrombocytopenia 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MECOM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42284358).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004991.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MECOM	NM_004991.4	MANE Select	c.3715G>T	p.Val1239Leu	missense	Exon 17 of 17	NP_004982.2	Q03112-3
MECOM	NM_001366466.2		c.3688G>T	p.Val1230Leu	missense	Exon 16 of 16	NP_001353395.1	Q03112-7
MECOM	NM_001105077.4		c.3346G>T	p.Val1116Leu	missense	Exon 17 of 17	NP_001098547.3	Q03112-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MECOM	ENST00000651503.2	MANE Select	c.3715G>T	p.Val1239Leu	missense	Exon 17 of 17	ENSP00000498411.1	Q03112-3
MECOM	ENST00000264674.7	TSL:1	c.3346G>T	p.Val1116Leu	missense	Exon 17 of 17	ENSP00000264674.3	Q03112-4
MECOM	ENST00000433243.6	TSL:1	c.3154G>T	p.Val1052Leu	missense	Exon 17 of 17	ENSP00000394302.2	A0A0C3SFZ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111938

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

0.00074

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.0057

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.036

MetaRNN

Benign

0.42

MetaSVM

Benign

-1.0

PhyloP100

7.4

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.23

REVEL

Benign

0.26

Sift

Benign

0.86

Sift4G

Benign

0.78

Polyphen

1.0

Vest4

0.65

MutPred

0.17

Loss of MoRF binding (P = 0.0887)

MVP

0.23

MPC

0.091

ClinPred

0.66

GERP RS

5.8

Varity_R

0.060

gMVP

0.50

Mutation Taster

=75/25

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over