chr3-169582431-C-T

Position:

• chr3-169582431-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MECOM	NM_004991.4	c.37+80905G>A		intron_variant		ENST00000651503.2	NP_004982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MECOM	ENST00000651503.2	c.37+80905G>A		intron_variant			NM_004991.4	ENSP00000498411	P3
MECOM	ENST00000485957.1	n.283+80905G>A		intron_variant, non_coding_transcript_variant		1
MECOM	ENST00000486748.2	c.38-16391G>A		intron_variant		5		ENSP00000419537
MECOM	ENST00000494292.6	c.37+80905G>A		intron_variant		5		ENSP00000417899	A1

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

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.226

Alfa AF: 0.212 Hom.: 5745

Bravo AF: 0.236

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.029
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1344555; hg19: chr3-169300219;