chr4-1332812-C-G

Variant names:

• chr4-1332812-C-G
• NM_001017405.3:c.712C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001017405.3(MAEA):​c.712C>G​(p.Gln238Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAEA NM_001017405.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3599445).

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.712C>G	p.Gln238Glu	missense	Exon 6 of 9	NP_001017405.1	Q7L5Y9-1
	MAEA	NM_001297432.2		c.709C>G	p.Gln237Glu	missense	Exon 6 of 9	NP_001284361.1	B4DVN3
	MAEA	NM_005882.5		c.589C>G	p.Gln197Glu	missense	Exon 5 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.712C>G	p.Gln238Glu	missense	Exon 6 of 9	ENSP00000302830.4	Q7L5Y9-1
	MAEA	ENST00000509531.5	TSL:1	n.512C>G		non_coding_transcript_exon	Exon 4 of 7	ENSP00000426966.1	D6RDW4
	MAEA	ENST00000868652.1		c.839C>G	p.Pro280Arg	missense	Exon 7 of 10	ENSP00000538711.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0078	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.97	T
PhyloP100		7.6
PROVEAN	Benign	2.6	N
REVEL	Benign	0.16
Sift	Uncertain	0.015	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.20	B
Vest4		0.51
MutPred		0.37		Gain of MoRF binding (P = 6e-04)
MVP		0.57
ClinPred		0.78	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
Mutation Taster		=58/42	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

hg19: chr4-1326600;