rs567208173

Variant names:

• chr1-151612258-TGGC-T
• rs567208173
• NM_001330723.2:c.69_71delCGG

Your query was ambiguous. Multiple possible variants found:

• chr1-151612258-TGGC-T
• chr1-151612258-TGGC-TGGCGGC
• chr1-151612258-TGGC-TGGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001330723.2(SNX27):​c.69_71delCGG​(p.Gly24del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000668 in 1,288,054 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G23G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: SNX27 NM_001330723.2 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89
• 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

ENSG00000250734 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001330723.2

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.69_71delCGG	p.Gly24del	disruptive_inframe_deletion	Exon 1 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.69_71delCGG	p.Gly24del	disruptive_inframe_deletion	Exon 1 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.69_71delCGG	p.Gly24del	disruptive_inframe_deletion	Exon 1 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.69_71delCGG	p.Gly24del	disruptive_inframe_deletion	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.69_71delCGG	p.Gly24del	disruptive_inframe_deletion	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368841.7	TSL:1	n.69_71delCGG		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000943 AC: 45 AN: 47704 AF XY: 0.00103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.000394

Gnomad EAS exome AF: 0.000519

Gnomad FIN exome AF: 0.000563

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.000858

GnomAD4 exome AF: 0.0000668 AC: 86 AN: 1288054 Hom.: 0 AF XY: 0.0000760 AC XY: 48 AN XY: 631698

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000384 AC: 1 AN: 26064

American (AMR) AF: 0.000512 AC: 9 AN: 17570

Ashkenazi Jewish (ASJ) AF: 0.0000508 AC: 1 AN: 19696

East Asian (EAS) AF: 0.0000696 AC: 2 AN: 28754

South Asian (SAS) AF: 0.000340 AC: 22 AN: 64682

European-Finnish (FIN) AF: 0.000142 AC: 6 AN: 42282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5066

European-Non Finnish (NFE) AF: 0.0000398 AC: 41 AN: 1030876

Other (OTH) AF: 0.0000754 AC: 4 AN: 53064

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9
Mutation Taster		=74/26	polymorphism

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: rs567208173; hg19: chr1-151584734;