1-151612207-G-A

Variant names:

• chr1-151612207-G-A
• rs2102578028
• NM_001330723.2:c.6G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330723.2(SNX27):​c.6G>A​(p.Ala2Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000251 in 1,195,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: SNX27 NM_001330723.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).

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.6G>A	p.Ala2Ala	synonymous	Exon 1 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.6G>A	p.Ala2Ala	synonymous	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.6G>A	p.Ala2Ala	synonymous	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368841.7	TSL:1	n.6G>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000251 AC: 3 AN: 1195070 Hom.: 0 Cov.: 31 AF XY: 0.00000173 AC XY: 1 AN XY: 577302

African (AFR) AF: 0.00 AC: 0 AN: 24122

American (AMR) AF: 0.00 AC: 0 AN: 10512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16538

East Asian (EAS) AF: 0.00 AC: 0 AN: 26950

South Asian (SAS) AF: 0.00 AC: 0 AN: 51412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4294

European-Non Finnish (NFE) AF: 0.00000306 AC: 3 AN: 979000

Other (OTH) AF: 0.00 AC: 0 AN: 48690

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.97
PhyloP100		5.1
PromoterAI		-0.72	Under-expression
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

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: rs2102578028; hg19: chr1-151584683;