1-151665939-G-T

Variant names:

• chr1-151665939-G-T
• rs778236794
• NM_001330723.2:c.913G>T

Variant summary

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

The NM_001330723.2(SNX27):​c.913G>T​(p.Ala305Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,444,546 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A305V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SNX27 NM_001330723.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08
• Publications: 3 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]

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=0.36551452).

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.913G>T	p.Ala305Ser	missense	Exon 6 of 12	NP_001317652.1
	SNX27	NM_030918.6		c.913G>T	p.Ala305Ser	missense	Exon 6 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.610G>T	p.Ala204Ser	missense	Exon 5 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.913G>T	p.Ala305Ser	missense	Exon 6 of 12	ENSP00000400333.2
	SNX27	ENST00000368843.8	TSL:1	c.913G>T	p.Ala305Ser	missense	Exon 6 of 12	ENSP00000357836.3
	SNX27	ENST00000368838.2	TSL:1	c.508G>T	p.Ala170Ser	missense	Exon 5 of 10	ENSP00000357831.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444546 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 718636

African (AFR) AF: 0.00 AC: 0 AN: 32948

American (AMR) AF: 0.00 AC: 0 AN: 43522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25726

East Asian (EAS) AF: 0.00 AC: 0 AN: 39010

South Asian (SAS) AF: 0.00 AC: 0 AN: 83798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101382

Other (OTH) AF: 0.0000168 AC: 1 AN: 59498

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.033
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N
PhyloP100		6.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.076
Sift	Benign	0.17	T
Sift4G	Benign	0.51	T
Polyphen		0.083	B
Vest4		0.62
MutPred		0.65		Loss of helix (P = 0.0196)
MVP		0.093
MPC		0.55
ClinPred		0.92	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.57
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs778236794; hg19: chr1-151638415;