NM_001330723.2:c.16G>C

Variant names:

• chr1-151612217-G-C
• rs1027134476
• NM_001330723.2:c.16G>C

Variant summary

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

The NM_001330723.2(SNX27):​c.16G>C​(p.Gly6Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000515 in 1,359,104 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. G6V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: SNX27 NM_001330723.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 6.38
• Publications: 1 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: 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.16G>C	p.Gly6Arg	missense	Exon 1 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.16G>C	p.Gly6Arg	missense	Exon 1 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.16G>C	p.Gly6Arg	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.16G>C	p.Gly6Arg	missense	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.16G>C	p.Gly6Arg	missense	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368841.7	TSL:1	n.16G>C		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000497 AC: 6 AN: 1206912 Hom.: 0 Cov.: 31 AF XY: 0.00000171 AC XY: 1 AN XY: 583934

African (AFR) AF: 0.000124 AC: 3 AN: 24288

American (AMR) AF: 0.0000897 AC: 1 AN: 11154

Ashkenazi Jewish (ASJ) AF: 0.0000593 AC: 1 AN: 16856

East Asian (EAS) AF: 0.00 AC: 0 AN: 27056

South Asian (SAS) AF: 0.00 AC: 0 AN: 53352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4472

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 984934

Other (OTH) AF: 0.00 AC: 0 AN: 49260

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	Severe myoclonic epilepsy in infancy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.4
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Polyphen		0.98	D
Vest4		0.55
MutPred		0.42		Gain of helix (P = 0.0496)
MVP		0.62
MPC		1.7
ClinPred		0.84	D
GERP RS		3.1
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.36
gMVP		0.68
Mutation Taster		=72/28	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: rs1027134476; hg19: chr1-151584693;