rs10513665

Variant names:

• chr3-169299492-G-A
• rs10513665
• NM_004991.4:c.375+81695C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-169299492-G-A
• chr3-169299492-G-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.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
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 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.375+81695C>T		intron	N/A	NP_004982.2
	MECOM	NM_001366466.2		c.375+81695C>T		intron	N/A	NP_001353395.1
	MECOM	NM_001205194.2		c.-189-155660C>T		intron	N/A	NP_001192123.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MECOM	ENST00000651503.2	MANE Select	c.375+81695C>T		intron	N/A	ENSP00000498411.1
	MECOM	ENST00000485957.1	TSL:1	n.621+81695C>T		intron	N/A
	MECOM	ENST00000494292.6	TSL:5	c.375+81695C>T		intron	N/A	ENSP00000417899.1

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

African (AFR) AF: 0.190 AC: 7861 AN: 41464

American (AMR) AF: 0.0260 AC: 398 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00894 AC: 31 AN: 3468

East Asian (EAS) AF: 0.0443 AC: 229 AN: 5172

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4814

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00703 AC: 478 AN: 68010

Other (OTH) AF: 0.0507 AC: 107 AN: 2112

Alfa AF: 0.0228 Hom.: 890

Bravo AF: 0.0685

Asia WGS AF: 0.0220 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.74
PhyloP100		-0.026
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: rs10513665; hg19: chr3-169017280;