rs779687444

Variant names:

• chr1-151660857-G-A
• rs779687444
• NM_001330723.2:c.796G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-151660857-G-A
• chr1-151660857-G-C
• chr1-151660857-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001330723.2(SNX27):​c.796G>A​(p.Asp266Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,608,312 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: SNX27 NM_001330723.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: 7.18
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29899243).
• BS2: High AC in GnomAdExome4 at 22 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.796G>A	p.Asp266Asn	missense	Exon 4 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.796G>A	p.Asp266Asn	missense	Exon 4 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.493G>A	p.Asp165Asn	missense	Exon 3 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.796G>A	p.Asp266Asn	missense	Exon 4 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.796G>A	p.Asp266Asn	missense	Exon 4 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368838.2	TSL:1	c.391G>A	p.Asp131Asn	missense	Exon 3 of 10	ENSP00000357831.2	A0A5H1ZRP6

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000239 AC: 6 AN: 251328 AF XY: 0.0000147

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: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1456114 Hom.: 0 Cov.: 27 AF XY: 0.0000179 AC XY: 13 AN XY: 724738

African (AFR) AF: 0.0000300 AC: 1 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39568

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86108

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000163 AC: 18 AN: 1106948

Other (OTH) AF: 0.00 AC: 0 AN: 60200

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15282

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: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000752 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.081
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.2
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.064
Sift	Benign	0.13	T
Sift4G	Benign	0.20	T
Polyphen		0.038	B
Vest4		0.45
MutPred		0.30		Gain of loop (P = 0.1069)
MVP		0.39
MPC		0.62
ClinPred		0.52	D
GERP RS		5.3
Varity_R		0.20
gMVP		0.50
Mutation Taster		=63/37	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: rs779687444; hg19: chr1-151633333;