rs763585979

Variant names:

• chr1-151612435-G-A
• rs763585979
• NM_001330723.2:c.234G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001330723.2(SNX27):​c.234G>A​(p.Leu78Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,468,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L78L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: SNX27 NM_001330723.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.89
• 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]

ENSG00000250734 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 1-151612435-G-A is Benign according to our data. Variant chr1-151612435-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 462813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.89 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 42 AD 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.234G>A	p.Leu78Leu	synonymous	Exon 1 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.234G>A	p.Leu78Leu	synonymous	Exon 1 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.234G>A	p.Leu78Leu	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.234G>A	p.Leu78Leu	synonymous	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.234G>A	p.Leu78Leu	synonymous	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368841.7	TSL:1	n.180+54G>A		intron	N/A	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000187 AC: 2 AN: 107008 AF XY: 0.0000169

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000725

Gnomad NFE exome AF: 0.0000195

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000319 AC: 42 AN: 1316334 Hom.: 0 Cov.: 31 AF XY: 0.0000263 AC XY: 17 AN XY: 645944

African (AFR) AF: 0.0000369 AC: 1 AN: 27088

American (AMR) AF: 0.0000427 AC: 1 AN: 23394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19470

East Asian (EAS) AF: 0.00 AC: 0 AN: 30980

South Asian (SAS) AF: 0.00 AC: 0 AN: 66198

European-Finnish (FIN) AF: 0.0000212 AC: 1 AN: 47132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5268

European-Non Finnish (NFE) AF: 0.0000374 AC: 39 AN: 1042910

Other (OTH) AF: 0.00 AC: 0 AN: 53894

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

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
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.97
PhyloP100		1.9
PromoterAI		0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs763585979; hg19: chr1-151584911;