3-169422102-T-C

Position:

• chr3-169422102-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004991.4(MECOM):​c.38-40578A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,924 control chromosomes in the GnomAD database, including 16,135 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 0.45 (16135 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MECOM	NM_004991.4	c.38-40578A>G		intron_variant		ENST00000651503.2	NP_004982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MECOM	ENST00000651503.2	c.38-40578A>G		intron_variant			NM_004991.4	ENSP00000498411.1
MECOM	ENST00000485957.1	n.284-40578A>G		intron_variant		1
MECOM	ENST00000494292.6	c.38-40578A>G		intron_variant		5		ENSP00000417899.1
MECOM	ENST00000486748.2	c.110-40578A>G		intron_variant		5		ENSP00000419537.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68797 AN: 151806 Hom.: 16119 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.453 AC: 68851 AN: 151924 Hom.: 16135 Cov.: 32 AF XY: 0.457 AC XY: 33895 AN XY: 74236

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.461

Alfa AF: 0.444 Hom.: 22758

Bravo AF: 0.460

Asia WGS AF: 0.547 AC: 1895 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1918969; hg19: chr3-169139890;