rs1354158738

Variant names:

• chr1-151612319-G-A
• rs1354158738
• NM_001330723.2:c.118G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-151612319-G-A
• chr1-151612319-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330723.2(SNX27):​c.118G>A​(p.Gly40Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000073 in 1,369,532 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 (★). Synonymous variant affecting the same amino acid position (i.e. G40G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SNX27 NM_001330723.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4213669).

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.118G>A	p.Gly40Ser	missense	Exon 1 of 12	NP_001317652.1
	SNX27	NM_030918.6		c.118G>A	p.Gly40Ser	missense	Exon 1 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.118G>A	p.Gly40Ser	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.118G>A	p.Gly40Ser	missense	Exon 1 of 12	ENSP00000400333.2
	SNX27	ENST00000368843.8	TSL:1	c.118G>A	p.Gly40Ser	missense	Exon 1 of 12	ENSP00000357836.3
	SNX27	ENST00000368841.7	TSL:1	n.118G>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1369532 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 676758

African (AFR) AF: 0.00 AC: 0 AN: 28424

American (AMR) AF: 0.00 AC: 0 AN: 29706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23524

East Asian (EAS) AF: 0.00 AC: 0 AN: 31214

South Asian (SAS) AF: 0.00 AC: 0 AN: 76188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 9.34e-7 AC: 1 AN: 1071164

Other (OTH) AF: 0.00 AC: 0 AN: 56796

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe myoclonic epilepsy in infancy Uncertain:1

Jun 27, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 462805). This variant has not been reported in the literature in individuals affected with SNX27-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 40 of the SNX27 protein (p.Gly40Ser). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.86	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.0
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.21
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.052	T
Polyphen		1.0	D
Vest4		0.42
MutPred		0.45		Gain of phosphorylation at G40 (P = 0.0174)
MVP		0.13
MPC		1.4
ClinPred		0.83	D
GERP RS		3.0
PromoterAI		-0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.50
gMVP		0.48
Mutation Taster		=58/42	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: rs1354158738; hg19: chr1-151584795;