4-1339092-C-G

Variant names:

• chr4-1339092-C-G
• rs749219110
• NM_001017405.3:c.1114C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017405.3(MAEA):​c.1114C>G​(p.Gln372Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q372K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MAEA NM_001017405.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87
• Publications: 0 publications found

Genes affected

MAEA (HGNC:13731): (macrophage erythroblast attacher, E3 ubiquitin ligase) This gene encodes a protein that mediates the attachment of erythroblasts to macrophages. This attachment promotes terminal maturation and enucleation of erythroblasts, presumably by suppressing apoptosis. The encoded protein is an integral membrane protein with the N-terminus on the extracellular side and the C-terminus on the cytoplasmic side of the cell. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14645371).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017405.3. 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
	MAEA	NM_001017405.3	MANE Select	c.1114C>G	p.Gln372Glu	missense	Exon 9 of 9	NP_001017405.1	Q7L5Y9-1
	MAEA	NM_001297432.2		c.1111C>G	p.Gln371Glu	missense	Exon 9 of 9	NP_001284361.1	B4DVN3
	MAEA	NM_005882.5		c.991C>G	p.Gln331Glu	missense	Exon 8 of 8	NP_005873.2	Q7L5Y9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAEA	ENST00000303400.9	TSL:1 MANE Select	c.1114C>G	p.Gln372Glu	missense	Exon 9 of 9	ENSP00000302830.4	Q7L5Y9-1
	MAEA	ENST00000509531.5	TSL:1	n.*176C>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000426966.1	D6RDW4
	MAEA	ENST00000509531.5	TSL:1	n.*176C>G		3_prime_UTR	Exon 7 of 7	ENSP00000426966.1	D6RDW4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.00071
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.095	N
PhyloP100		5.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.080
Sift	Benign	0.64	T
Sift4G	Benign	1.0	T
Polyphen		0.040	B
Vest4		0.37
MutPred		0.45		Loss of catalytic residue at Q410 (P = 0.0071)
MVP		0.23
MPC		1.2
ClinPred		0.49	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.34
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs749219110; hg19: chr4-1332880;