rs10513665

Positions:

• chr3-169299492-G-A

Variant summary

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

The NM_004991.4(MECOM):​c.375+81695C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 152,148 control chromosomes in the GnomAD database, including 782 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 0.061 (782 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MECOM	NM_004991.4	c.375+81695C>T		intron_variant		ENST00000651503.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECOM	ENST00000651503.2	c.375+81695C>T		intron_variant			NM_004991.4	P3
MECOM	ENST00000485957.1	n.621+81695C>T		intron_variant, non_coding_transcript_variant		1
MECOM	ENST00000494292.6	c.375+81695C>T		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9222 AN: 152030 Hom.: 780 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00706

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0607 AC: 9229 AN: 152148 Hom.: 782 Cov.: 32 AF XY: 0.0583 AC XY: 4340 AN XY: 74404

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.0260

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.0443

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00703

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0143 Hom.: 176

Bravo AF: 0.0685

Asia WGS AF: 0.0220 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10513665; hg19: chr3-169017280;