NM_002436.4:c.689G>A

Variant names:

• chrX-154785146-C-T
• NM_002436.4:c.689G>A

Variant summary

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

The NM_002436.4(MPP1):​c.689G>A​(p.Ser230Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: MPP1 NM_002436.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56
• Publications: 0 publications found

Genes affected

MPP1 (HGNC:7219): (MAGUK p55 scaffold protein 1) This gene encodes the prototype of the membrane-associated guanylate kinase (MAGUK) family proteins. MAGUKs interact with the cytoskeleton and regulate cell proliferation, signaling pathways, and intercellular junctions. The encoded protein is an extensively palmitoylated membrane phosphoprotein containing a PDZ domain, a Src homology 3 (SH3) motif, and a guanylate kinase domain. This gene product interacts with various cytoskeletal proteins and cell junctional proteins in different tissue and cell types, and may be involved in the regulation of cell shape, hair cell development, neural patterning of the retina, and apico-basal polarity and tumor suppression pathways in non-erythroid cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

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=0.33340037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002436.4. 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
	MPP1	NM_002436.4	MANE Select	c.689G>A	p.Ser230Asn	missense	Exon 7 of 12	NP_002427.1	Q00013-1
	MPP1	NM_001166460.2		c.638G>A	p.Ser213Asn	missense	Exon 7 of 12	NP_001159932.1
	MPP1	NM_001166461.2		c.629G>A	p.Ser210Asn	missense	Exon 7 of 12	NP_001159933.1	Q00013-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP1	ENST00000369534.8	TSL:1 MANE Select	c.689G>A	p.Ser230Asn	missense	Exon 7 of 12	ENSP00000358547.3	Q00013-1
	MPP1	ENST00000393531.5	TSL:1	c.629G>A	p.Ser210Asn	missense	Exon 7 of 12	ENSP00000377165.1	Q00013-3
	MPP1	ENST00000475943.5	TSL:1	n.415G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

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	0.23
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.22	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.6	L
PhyloP100		4.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.34
Sift	Benign	0.31	T
Sift4G	Benign	0.30	T
Polyphen		0.10	B
Vest4		0.48
MutPred		0.22		Loss of phosphorylation at S230 (P = 0.0168)
MVP		0.85
MPC		1.1
ClinPred		0.73	D
GERP RS		5.6
Varity_R		0.46
gMVP		0.70
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chrX-154013421; COSMIC: COSV65728017; COSMIC: COSV65728017;