3-169582431-C-T

Variant names:

• chr3-169582431-C-T
• rs1344555
• NM_004991.4:c.37+80905G>A

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+80905G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,772 control chromosomes in the GnomAD database, including 4,892 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 0.23 (4892 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10
• Publications: 37 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), G2P, Ambry Genetics
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MECOM	NM_004991.4	MANE Select	c.37+80905G>A		intron	N/A	NP_004982.2	Q03112-3
	MECOM	NM_001366466.2		c.37+80905G>A		intron	N/A	NP_001353395.1	Q03112-7
	MECOM	NM_001205194.2		c.-190+80905G>A		intron	N/A	NP_001192123.1	Q03112-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MECOM	ENST00000651503.2	MANE Select	c.37+80905G>A		intron	N/A	ENSP00000498411.1	Q03112-3
	MECOM	ENST00000485957.1	TSL:1	n.283+80905G>A		intron	N/A
	MECOM	ENST00000494292.6	TSL:5	c.37+80905G>A		intron	N/A	ENSP00000417899.1	Q03112-7

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35035 AN: 151652 Hom.: 4882 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.231 AC: 35096 AN: 151772 Hom.: 4892 Cov.: 32 AF XY: 0.241 AC XY: 17873 AN XY: 74170

African (AFR) AF: 0.204 AC: 8447 AN: 41376

American (AMR) AF: 0.309 AC: 4707 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3464

East Asian (EAS) AF: 0.690 AC: 3562 AN: 5160

South Asian (SAS) AF: 0.315 AC: 1514 AN: 4800

European-Finnish (FIN) AF: 0.266 AC: 2794 AN: 10514

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12838 AN: 67900

Other (OTH) AF: 0.226 AC: 476 AN: 2108

Alfa AF: 0.212 Hom.: 7999

Bravo AF: 0.236

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.029
DANN	Benign	0.62
PhyloP100		-3.1
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: rs1344555; hg19: chr3-169300219;