rs954308263

Variant names:

• chr1-151612218-G-A
• rs954308263
• NM_001330723.2:c.17G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-151612218-G-A
• chr1-151612218-G-C
• chr1-151612218-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001330723.2(SNX27):​c.17G>A​(p.Gly6Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000584 in 1,370,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G6R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: SNX27 NM_001330723.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.36
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 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.17G>A	p.Gly6Glu	missense	Exon 1 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.17G>A	p.Gly6Glu	missense	Exon 1 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.17G>A	p.Gly6Glu	missense	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.17G>A	p.Gly6Glu	missense	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.17G>A	p.Gly6Glu	missense	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368841.7	TSL:1	n.17G>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152190 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

GnomAD4 exome AF: 0.00000492 AC: 6 AN: 1218672 Hom.: 0 Cov.: 31 AF XY: 0.00000508 AC XY: 3 AN XY: 590812

African (AFR) AF: 0.0000409 AC: 1 AN: 24458

American (AMR) AF: 0.00 AC: 0 AN: 11910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17170

East Asian (EAS) AF: 0.0000368 AC: 1 AN: 27198

South Asian (SAS) AF: 0.0000362 AC: 2 AN: 55280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4580

European-Non Finnish (NFE) AF: 0.00000202 AC: 2 AN: 992214

Other (OTH) AF: 0.00 AC: 0 AN: 49786

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

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
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.4
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		0.87	P
Vest4		0.53
MutPred		0.41		Gain of solvent accessibility (P = 0.0374)
MVP		0.54
MPC		1.8
ClinPred		0.76	D
GERP RS		3.1
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.39
gMVP		0.66
Mutation Taster		=75/25	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: rs954308263; hg19: chr1-151584694;