NM_004991.4:c.38-113055A>C

Variant names:

• chr3-169494579-T-G
• rs7638569
• NM_004991.4:c.38-113055A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004991.4(MECOM):​c.38-113055A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,144 control chromosomes in the GnomAD database, including 52,498 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 0.82 (52498 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 7 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

ENSG00000302206 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MECOM	NM_004991.4	c.38-113055A>C		intron_variant	Intron 1 of 16	ENST00000651503.2	NP_004982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MECOM	ENST00000651503.2	c.38-113055A>C		intron_variant	Intron 1 of 16		NM_004991.4	ENSP00000498411.1

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124268 AN: 152026 Hom.: 52494 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.817 AC: 124304 AN: 152144 Hom.: 52498 Cov.: 32 AF XY: 0.823 AC XY: 61201 AN XY: 74392

African (AFR) AF: 0.579 AC: 23980 AN: 41446

American (AMR) AF: 0.843 AC: 12878 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3025 AN: 3472

East Asian (EAS) AF: 0.907 AC: 4692 AN: 5174

South Asian (SAS) AF: 0.943 AC: 4551 AN: 4824

European-Finnish (FIN) AF: 0.950 AC: 10088 AN: 10616

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62215 AN: 68008

Other (OTH) AF: 0.833 AC: 1762 AN: 2114

Alfa AF: 0.876 Hom.: 211122

Bravo AF: 0.797

Asia WGS AF: 0.891 AC: 3099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.49
PhyloP100		-0.25
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: rs7638569; hg19: chr3-169212367;