1-151666010-T-G

Variant names:

• chr1-151666010-T-G
• NM_001330723.2:c.984T>G
• SNX27 p.Phe328Leu

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001330723.2(SNX27):​c.984T>G​(p.Phe328Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F328F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX27 NM_001330723.2 missense, splice_region
• Scores: Splicing: ADA: 0.1244
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

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.984T>G	p.Phe328Leu	missense splice_region	Exon 6 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.984T>G	p.Phe328Leu	missense splice_region	Exon 6 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.681T>G	p.Phe227Leu	missense splice_region	Exon 5 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.984T>G	p.Phe328Leu	missense splice_region	Exon 6 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.984T>G	p.Phe328Leu	missense splice_region	Exon 6 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368838.2	TSL:1	c.579T>G	p.Phe193Leu	missense splice_region	Exon 5 of 10	ENSP00000357831.2	A0A5H1ZRP6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.4
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.011	D
Varity_R		0.51
gMVP		0.62
Mutation Taster		=5/95	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.12
dbscSNV1_RF	Benign	0.21
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-151638486;