NM_002436.4:c.152G>A

Variant names:

• chrX-154792236-C-T
• rs782318569
• NM_002436.4:c.152G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002436.4(MPP1):​c.152G>A​(p.Gly51Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000504 in 1,210,343 control chromosomes in the GnomAD database, including 1 homozygotes. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G51G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.000051 (1 hom. 21 hem.)
• Consequence: MPP1 NM_002436.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019574374).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

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.152G>A	p.Gly51Glu	missense	Exon 2 of 12	NP_002427.1	Q00013-1
	MPP1	NM_001166460.2		c.152G>A	p.Gly51Glu	missense	Exon 2 of 12	NP_001159932.1
	MPP1	NM_001166461.2		c.152G>A	p.Gly51Glu	missense	Exon 2 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.152G>A	p.Gly51Glu	missense	Exon 2 of 12	ENSP00000358547.3	Q00013-1
	MPP1	ENST00000393531.5	TSL:1	c.152G>A	p.Gly51Glu	missense	Exon 2 of 12	ENSP00000377165.1	Q00013-3
	MPP1	ENST00000475943.5	TSL:1	n.207-5836G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000534 AC: 6 AN: 112279 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000187

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00148

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000153 AC: 28 AN: 182675 AF XY: 0.000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000443

GnomAD4 exome AF: 0.0000510 AC: 56 AN: 1098011 Hom.: 1 Cov.: 30 AF XY: 0.0000578 AC XY: 21 AN XY: 363377

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.000312 AC: 11 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.000739 AC: 40 AN: 54134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40489

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841975

Other (OTH) AF: 0.0000651 AC: 3 AN: 46089

GnomAD4 genome AF: 0.0000445 AC: 5 AN: 112332 Hom.: 0 Cov.: 23 AF XY: 0.0000580 AC XY: 2 AN XY: 34492

African (AFR) AF: 0.00 AC: 0 AN: 30931

American (AMR) AF: 0.000187 AC: 2 AN: 10680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3573

South Asian (SAS) AF: 0.00111 AC: 3 AN: 2703

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53193

Other (OTH) AF: 0.00 AC: 0 AN: 1524

Alfa AF: 0.0000262 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.000157 AC: 19

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	0.31
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.64
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.15
Sift	Benign	0.048	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.069
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.59
MPC		1.6
ClinPred		0.043	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.18
gMVP		0.90
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs782318569; hg19: chrX-154020511; COSMIC: COSV65728961; COSMIC: COSV65728961;