NM_001330723.2:c.41C>G

Variant names:

• chr1-151612242-C-G
• rs965328686
• NM_001330723.2:c.41C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330723.2(SNX27):​c.41C>G​(p.Pro14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P14S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX27 NM_001330723.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29
• 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]

ENSG00000250734 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18923908).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX27	NM_001330723.2	MANE Select	c.41C>G	p.Pro14Arg	missense	Exon 1 of 12	NP_001317652.1
	SNX27	NM_030918.6		c.41C>G	p.Pro14Arg	missense	Exon 1 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.41C>G	p.Pro14Arg	missense	Exon 1 of 11	NP_001424530.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX27	ENST00000458013.7	TSL:5 MANE Select	c.41C>G	p.Pro14Arg	missense	Exon 1 of 12	ENSP00000400333.2
	SNX27	ENST00000368843.8	TSL:1	c.41C>G	p.Pro14Arg	missense	Exon 1 of 12	ENSP00000357836.3
	SNX27	ENST00000368841.7	TSL:1	n.41C>G		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.3
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.040
Sift	Uncertain	0.018	D
Sift4G	Benign	0.65	T
Polyphen		0.054	B
Vest4		0.17
MutPred		0.29		Gain of methylation at R16 (P = 0.0446)
MVP		0.082
MPC		0.62
ClinPred		0.77	D
GERP RS		3.9
PromoterAI		0.24	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.62
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: rs965328686; hg19: chr1-151584718;