rs1553266166

Variant names:

• chr1-151692548-T-TA
• rs1553266166
• NM_001330723.2:c.1356dupA

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001330723.2(SNX27):​c.1356dupA​(p.Leu453ThrfsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SNX27 NM_001330723.2 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.37
• Publications: 0 publications found

Genes affected

SNX27 (HGNC:20073): (sorting nexin 27) This gene encodes a member of the sorting nexin family, a diverse group of cytoplasmic and membrane-associated proteins involved in endocytosis of plasma membrane receptors and protein trafficking through these compartments. All members of this protein family contain a phosphoinositide binding domain (PX domain). A highly similar protein in mouse is responsible for the specific recruitment of an isoform of serotonin 5-hydroxytryptamine 4 receptor into early endosomes, suggesting the analogous role for the human protein. [provided by RefSeq, Jul 2008]

SNX27 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-151692548-T-TA is Pathogenic according to our data. Variant chr1-151692548-T-TA is described in ClinVar as Pathogenic. ClinVar VariationId is 462810.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330723.2. 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
	SNX27	NM_001330723.2	MANE Select	c.1356dupA	p.Leu453ThrfsTer6	frameshift	Exon 9 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.1356dupA	p.Leu453ThrfsTer6	frameshift	Exon 9 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.1053dupA	p.Leu352ThrfsTer6	frameshift	Exon 8 of 11	NP_001424530.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX27	ENST00000458013.7	TSL:5 MANE Select	c.1356dupA	p.Leu453ThrfsTer6	frameshift	Exon 9 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.1356dupA	p.Leu453ThrfsTer6	frameshift	Exon 9 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368838.2	TSL:1	c.951dupA	p.Leu318fs	frameshift	Exon 8 of 10	ENSP00000357831.2	A0A5H1ZRP6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Severe myoclonic epilepsy in infancy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.4
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1553266166; hg19: chr1-151665024;