rs5987027

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002436.4(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 NM_002436.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP1	NM_002436.4	c.677+372G>A		intron_variant	Intron 6 of 11	ENST00000369534.8	NP_002427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP1	ENST00000369534.8	c.677+372G>A		intron_variant	Intron 6 of 11	1	NM_002436.4	ENSP00000358547.3

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 8182 AN: 112092 Hom.: 736 Cov.: 23 AF XY: 0.0659 AC XY: 2258 AN XY: 34282

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

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000735

Gnomad4 FIN AF: 0.000324

Gnomad4 NFE AF: 0.000582

Gnomad4 OTH AF: 0.0541

Alfa AF: 0.0162 Hom.: 464

Bravo AF: 0.0830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs5987027; hg19: chrX-154014107;