NM_001330723.2:c.14A>C

Variant names:

• chr1-151612215-A-C
• rs1667204535
• NM_001330723.2:c.14A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001330723.2(SNX27):​c.14A>C​(p.Asp5Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000125 in 1,204,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. D5E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SNX27 NM_001330723.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19556883).
• BS2: High AC in GnomAdExome4 at 15 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.14A>C	p.Asp5Ala	missense	Exon 1 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.14A>C	p.Asp5Ala	missense	Exon 1 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.14A>C	p.Asp5Ala	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.14A>C	p.Asp5Ala	missense	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.14A>C	p.Asp5Ala	missense	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368841.7	TSL:1	n.14A>C		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000125 AC: 15 AN: 1204072 Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 8 AN XY: 582382

African (AFR) AF: 0.00 AC: 0 AN: 24240

American (AMR) AF: 0.00 AC: 0 AN: 10980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16780

East Asian (EAS) AF: 0.00 AC: 0 AN: 27034

South Asian (SAS) AF: 0.00 AC: 0 AN: 52916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4256

European-Non Finnish (NFE) AF: 0.0000152 AC: 15 AN: 983644

Other (OTH) AF: 0.00 AC: 0 AN: 49136

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

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	0.073
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.7
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.081
Sift	Benign	0.038	D
Sift4G	Uncertain	0.055	T
Polyphen		0.0	B
Vest4		0.062
MutPred		0.26		Loss of solvent accessibility (P = 0.0169)
MVP		0.11
MPC		0.74
ClinPred		0.51	D
GERP RS		2.9
PromoterAI		0.019	Neutral
Varity_R		0.21
gMVP		0.39
Mutation Taster		=87/13	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: rs1667204535; hg19: chr1-151584691;