X-154783515-G-A

Variant names:

• chrX-154783515-G-A
• rs1603429916
• NM_002436.4:c.866-8C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002436.4(MPP1):​c.866-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000928 in 1,077,589 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: MPP1 NM_002436.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001636
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.122
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-154783515-G-A is Benign according to our data. Variant chrX-154783515-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 735927.Status of the report is criteria_provided_single_submitter, 1 stars.

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.866-8C>T		splice_region intron	N/A	NP_002427.1	Q00013-1
	MPP1	NM_001166460.2		c.815-8C>T		splice_region intron	N/A	NP_001159932.1
	MPP1	NM_001166461.2		c.806-8C>T		splice_region intron	N/A	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.866-8C>T		splice_region intron	N/A	ENSP00000358547.3	Q00013-1
	MPP1	ENST00000393531.5	TSL:1	c.806-8C>T		splice_region intron	N/A	ENSP00000377165.1	Q00013-3
	MPP1	ENST00000934478.1		c.866-8C>T		splice_region intron	N/A	ENSP00000604537.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.28e-7 AC: 1 AN: 1077589 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 343835

African (AFR) AF: 0.0000384 AC: 1 AN: 26018

American (AMR) AF: 0.00 AC: 0 AN: 34770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19142

East Asian (EAS) AF: 0.00 AC: 0 AN: 30065

South Asian (SAS) AF: 0.00 AC: 0 AN: 52850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4085

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 825188

Other (OTH) AF: 0.00 AC: 0 AN: 45395

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.0
DANN	Benign	0.57
PhyloP100		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.018
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: rs1603429916; hg19: chrX-154011790;