rs1343036

Variant names:

• chr3-169524458-G-A
• rs1343036
• NM_004991.4:c.37+138878C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004991.4(MECOM):​c.37+138878C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,106 control chromosomes in the GnomAD database, including 4,226 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4226 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MECOM	NM_004991.4	c.37+138878C>T		intron_variant	Intron 1 of 16	ENST00000651503.2	NP_004982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MECOM	ENST00000651503.2	c.37+138878C>T		intron_variant	Intron 1 of 16		NM_004991.4	ENSP00000498411.1
MECOM	ENST00000485957.1	n.283+138878C>T		intron_variant	Intron 1 of 2	1
MECOM	ENST00000494292.6	c.37+138878C>T		intron_variant	Intron 1 of 15	5		ENSP00000417899.1
MECOM	ENST00000486748.2	c.109+41511C>T		intron_variant	Intron 2 of 2	5		ENSP00000419537.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32424 AN: 151988 Hom.: 4229 Cov.: 32

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.213 AC: 32409 AN: 152106 Hom.: 4226 Cov.: 32 AF XY: 0.211 AC XY: 15670 AN XY: 74332

African (AFR) AF: 0.0732 AC: 3042 AN: 41550

American (AMR) AF: 0.215 AC: 3287 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3468

East Asian (EAS) AF: 0.136 AC: 703 AN: 5172

South Asian (SAS) AF: 0.146 AC: 704 AN: 4826

European-Finnish (FIN) AF: 0.292 AC: 3089 AN: 10562

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.295 AC: 20009 AN: 67930

Other (OTH) AF: 0.230 AC: 486 AN: 2116

Alfa AF: 0.230 Hom.: 878

Bravo AF: 0.205

Asia WGS AF: 0.138 AC: 482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.015
DANN	Benign	0.33
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1343036; hg19: chr3-169242246;