1-151612258-TGGC-TGGCGGC

Variant names:

• chr1-151612258-T-TGGC
• rs567208173
• NM_001330723.2:c.69_71dupCGG

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_001330723.2(SNX27):​c.69_71dupCGG​(p.Gly24dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,440,430 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G24G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0043 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (14 hom.)
• Consequence: SNX27 NM_001330723.2 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.07
• 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: Benign. The variant received -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001330723.2
• BP6: Variant 1-151612258-T-TGGC is Benign according to our data. Variant chr1-151612258-T-TGGC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 462816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00425 (645/151608) while in subpopulation NFE AF = 0.00579 (393/67830). AF 95% confidence interval is 0.00532. There are 2 homozygotes in GnomAd4. There are 345 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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_71dupCGG	p.Gly24dup	disruptive_inframe_insertion	Exon 1 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.69_71dupCGG	p.Gly24dup	disruptive_inframe_insertion	Exon 1 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.69_71dupCGG	p.Gly24dup	disruptive_inframe_insertion	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_71dupCGG	p.Gly24dup	disruptive_inframe_insertion	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.69_71dupCGG	p.Gly24dup	disruptive_inframe_insertion	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368841.7	TSL:1	n.69_71dupCGG		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes AF: 0.00426 AC: 645 AN: 151502 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000995

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00579

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.00373 AC: 178 AN: 47704 AF XY: 0.00342

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000743

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0120

Gnomad NFE exome AF: 0.00301

Gnomad OTH exome AF: 0.00600

GnomAD4 exome AF: 0.00421 AC: 5420 AN: 1288822 Hom.: 14 Cov.: 31 AF XY: 0.00423 AC XY: 2675 AN XY: 632138

African (AFR) AF: 0.000537 AC: 14 AN: 26070

American (AMR) AF: 0.000966 AC: 17 AN: 17594

Ashkenazi Jewish (ASJ) AF: 0.00325 AC: 64 AN: 19716

East Asian (EAS) AF: 0.00 AC: 0 AN: 28756

South Asian (SAS) AF: 0.00125 AC: 81 AN: 64818

European-Finnish (FIN) AF: 0.0147 AC: 623 AN: 42344

Middle Eastern (MID) AF: 0.00118 AC: 6 AN: 5066

European-Non Finnish (NFE) AF: 0.00430 AC: 4437 AN: 1031366

Other (OTH) AF: 0.00335 AC: 178 AN: 53092

GnomAD4 genome AF: 0.00425 AC: 645 AN: 151608 Hom.: 2 Cov.: 32 AF XY: 0.00466 AC XY: 345 AN XY: 74098

African (AFR) AF: 0.000992 AC: 41 AN: 41312

American (AMR) AF: 0.000917 AC: 14 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3462

East Asian (EAS) AF: 0.000390 AC: 2 AN: 5122

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4794

European-Finnish (FIN) AF: 0.0169 AC: 178 AN: 10512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00579 AC: 393 AN: 67830

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00261 Hom.: 0

Bravo AF: 0.00306

Asia WGS AF: 0.000870 AC: 3 AN: 3462

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Severe myoclonic epilepsy in infancy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=85/15	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs567208173; hg19: chr1-151584734; COSMIC: COSV104684854; COSMIC: COSV104684854;