rs10936578

Variant names:

• chr3-169313343-G-A
• rs10936578
• NM_004991.4:c.375+67844C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-169313343-G-A
• chr3-169313343-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+67844C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,194 control chromosomes in the GnomAD database, including 2,157 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 0.14 (2157 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MECOM	NM_004991.4	c.375+67844C>T		intron_variant	Intron 2 of 16	ENST00000651503.2	NP_004982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MECOM	ENST00000651503.2	c.375+67844C>T		intron_variant	Intron 2 of 16		NM_004991.4	ENSP00000498411.1
MECOM	ENST00000485957.1	n.621+67844C>T		intron_variant	Intron 2 of 2	1
MECOM	ENST00000494292.6	c.375+67844C>T		intron_variant	Intron 2 of 15	5		ENSP00000417899.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21296 AN: 152076 Hom.: 2156 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.140 AC: 21306 AN: 152194 Hom.: 2157 Cov.: 32 AF XY: 0.139 AC XY: 10313 AN XY: 74422

African (AFR) AF: 0.260 AC: 10768 AN: 41478

American (AMR) AF: 0.0806 AC: 1233 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 306 AN: 3470

East Asian (EAS) AF: 0.377 AC: 1947 AN: 5162

South Asian (SAS) AF: 0.101 AC: 486 AN: 4822

European-Finnish (FIN) AF: 0.0597 AC: 634 AN: 10620

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5538 AN: 68022

Other (OTH) AF: 0.139 AC: 293 AN: 2114

Alfa AF: 0.0817 Hom.: 396

Bravo AF: 0.148

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.43
PhyloP100		0.17
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: rs10936578; hg19: chr3-169031131;