rs5987027

Variant names:

• chrX-154785832-C-T
• rs5987027
• NM_002436.4:c.677+372G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369534.8(MPP1):​c.677+372G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 112,144 control chromosomes in the GnomAD database, including 736 homozygotes. There are 2,264 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.073 (736 hom., 2264 hem., cov: 23)
• Consequence: MPP1 ENST00000369534.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369534.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP1	NM_002436.4	MANE Select	c.677+372G>A		intron	N/A	NP_002427.1
	MPP1	NM_001166460.2		c.626+372G>A		intron	N/A	NP_001159932.1
	MPP1	NM_001166461.2		c.617+372G>A		intron	N/A	NP_001159933.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP1	ENST00000369534.8	TSL:1 MANE Select	c.677+372G>A		intron	N/A	ENSP00000358547.3
	MPP1	ENST00000393531.5	TSL:1	c.617+372G>A		intron	N/A	ENSP00000377165.1
	MPP1	ENST00000475943.5	TSL:1	n.403+372G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 8182 AN: 112092 Hom.: 736 Cov.: 23

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00110

Gnomad FIN AF: 0.000324

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.000582

Gnomad OTH AF: 0.0548

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0730 AC: 8189 AN: 112144 Hom.: 736 Cov.: 23 AF XY: 0.0659 AC XY: 2264 AN XY: 34344

African (AFR) AF: 0.254 AC: 7788 AN: 30641

American (AMR) AF: 0.0265 AC: 282 AN: 10651

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3592

South Asian (SAS) AF: 0.000735 AC: 2 AN: 2720

European-Finnish (FIN) AF: 0.000324 AC: 2 AN: 6171

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.000582 AC: 31 AN: 53283

Other (OTH) AF: 0.0541 AC: 83 AN: 1533

Alfa AF: 0.0483 Hom.: 2819

Bravo AF: 0.0830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.83
PhyloP100		0.0010
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs5987027; hg19: chrX-154014107;