chr4-1336979-C-T

Variant names:

• chr4-1336979-C-T
• NM_001017405.3:c.884C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001017405.3(MAEA):​c.884C>T​(p.Ser295Leu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAEA NM_001017405.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.66
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873

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.884C>T	p.Ser295Leu	missense	Exon 7 of 9	NP_001017405.1	Q7L5Y9-1
	MAEA	NM_001297432.2		c.881C>T	p.Ser294Leu	missense	Exon 7 of 9	NP_001284361.1	B4DVN3
	MAEA	NM_005882.5		c.761C>T	p.Ser254Leu	missense	Exon 6 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.884C>T	p.Ser295Leu	missense	Exon 7 of 9	ENSP00000302830.4	Q7L5Y9-1
	MAEA	ENST00000509531.5	TSL:1	n.684C>T		non_coding_transcript_exon	Exon 5 of 7	ENSP00000426966.1	D6RDW4
	MAEA	ENST00000505177.6	TSL:5	c.998C>T	p.Ser333Leu	missense	Exon 8 of 10	ENSP00000422215.2	E7ESC7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.7
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.87	P
Vest4		0.95
MutPred		0.54		Loss of disorder (P = 0.0519)
MVP		0.86
MPC		1.6
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.65
gMVP		0.87
Mutation Taster		=19/81	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr4-1330767;