rs143824239

Variant names:

• chrX-154792207-C-A
• rs143824239
• NM_002436.4:c.181G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002436.4(MPP1):​c.181G>T​(p.Val61Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,210,227 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 102 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., 52 hem., cov: 23)
  • Exomes 𝑓: 0.00017 (0 hom. 50 hem.)
• Consequence: MPP1 NM_002436.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0970
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002958268).
• BP6: Variant X-154792207-C-A is Benign according to our data. Variant chrX-154792207-C-A is described in ClinVar as Benign. ClinVar VariationId is 727529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 52 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.181G>T	p.Val61Phe	missense	Exon 2 of 12	NP_002427.1	Q00013-1
	MPP1	NM_001166460.2		c.181G>T	p.Val61Phe	missense	Exon 2 of 12	NP_001159932.1
	MPP1	NM_001166461.2		c.181G>T	p.Val61Phe	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.181G>T	p.Val61Phe	missense	Exon 2 of 12	ENSP00000358547.3	Q00013-1
	MPP1	ENST00000393531.5	TSL:1	c.181G>T	p.Val61Phe	missense	Exon 2 of 12	ENSP00000377165.1	Q00013-3
	MPP1	ENST00000475943.5	TSL:1	n.207-5807G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 184 AN: 112212 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000469

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00265

GnomAD2 exomes AF: 0.000405 AC: 74 AN: 182848 AF XY: 0.000252

Gnomad AFR exome AF: 0.00533

Gnomad AMR exome AF: 0.000146

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: 0.00

GnomAD4 exome AF: 0.000168 AC: 185 AN: 1097961 Hom.: 0 Cov.: 30 AF XY: 0.000138 AC XY: 50 AN XY: 363327

African (AFR) AF: 0.00633 AC: 167 AN: 26392

American (AMR) AF: 0.000170 AC: 6 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54137

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841914

Other (OTH) AF: 0.000239 AC: 11 AN: 46085

GnomAD4 genome AF: 0.00163 AC: 183 AN: 112266 Hom.: 0 Cov.: 23 AF XY: 0.00151 AC XY: 52 AN XY: 34426

African (AFR) AF: 0.00564 AC: 174 AN: 30827

American (AMR) AF: 0.000469 AC: 5 AN: 10672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3574

South Asian (SAS) AF: 0.00 AC: 0 AN: 2699

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6170

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53236

Other (OTH) AF: 0.00262 AC: 4 AN: 1527

Alfa AF: 0.000538 Hom.: 26

Bravo AF: 0.00189

ESP6500AA AF: 0.00443 AC: 17

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000412 AC: 50

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.13
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.097
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.0070
Sift	Benign	0.98	T
Sift4G	Benign	0.80	T
Polyphen		0.0010	B
Vest4		0.18
MVP		0.22
MPC		0.65
ClinPred		0.0064	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.46
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs143824239; hg19: chrX-154020482;