chr1-151612201-G-GAAGGGACATAGTAATTTCCGTTGTTTCATGTTCTAATCTGTATATGGAAGTTTCATTGACAAGCTCATAAAATGGCAGTTCCACACAACTTTGGGAAGCAATAATTTACATTATTAAAATTATCCTGAAA

Position:

• chr1-151612201-G-GAAGGGACATAGTAATTTCCGTTGTTTCATGTTCTAATCTGTATATGGAAGTTTCATTGACAAGCTCATAAAATGGCAGTTCCACACAACTTTGGGAAGCAATAATTTACATTATTAAAATTATCCTGAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001330723.2(SNX27):​c.1_2insAGGGACATAGTAATTTCCGTTGTTTCATGTTCTAATCTGTATATGGAAGTTTCATTGACAAGCTCATAAAATGGCAGTTCCACACAACTTTGGGAAGCAATAATTTACATTATTAAAATTATCCTGAAAA​(p.Met1LysfsTer?) variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX27 NM_001330723.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX27	NM_001330723.2	c.1_2insAGGGACATAGTAATTTCCGTTGTTTCATGTTCTAATCTGTATATGGAAGTTTCATTGACAAGCTCATAAAATGGCAGTTCCACACAACTTTGGGAAGCAATAATTTACATTATTAAAATTATCCTGAAAA	p.Met1LysfsTer?	5_prime_UTR_variant	1/12	ENST00000458013.7
LOC124904420	XR_007066622.1	n.376_377insTTTCAGGATAATTTTAATAATGTAAATTATTGCTTCCCAAAGTTGTGTGGAACTGCCATTTTATGAGCTTGTCAATGAAACTTCCATATACAGATTAGAACATGAAACAACGGAAATTACTATGTCCCTT		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX27	ENST00000458013.7	c.1_2insAGGGACATAGTAATTTCCGTTGTTTCATGTTCTAATCTGTATATGGAAGTTTCATTGACAAGCTCATAAAATGGCAGTTCCACACAACTTTGGGAAGCAATAATTTACATTATTAAAATTATCCTGAAAA	p.Met1LysfsTer?	5_prime_UTR_variant	1/12	5	NM_001330723.2	P1
	ENST00000504583.2	n.371_372insTTTCAGGATAATTTTAATAATGTAAATTATTGCTTCCCAAAGTTGTGTGGAACTGCCATTTTATGAGCTTGTCAATGAAACTTCCATATACAGATTAGAACATGAAACAACGGAAATTACTATGTCCCTT		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe myoclonic epilepsy in infancy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2021

This sequence change affects the initiator methionine of the SNX27 mRNA. The next in-frame methionine is located at codon 187. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with SNX27-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-151584677;